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Bupropion; Naltrexone

Indications/Dosage

Labeled

  • obesity
  • weight management

Off-Label

    † Off-label indication

    For the treatment of obesity and for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity

    Oral dosage (extended-release tablets)

    Adults

    Titrate to target dose during the first 4 weeks of treatment, as follows: WEEK 1) 1 tablet (8 mg naltrexone/90 mg bupropion) PO once daily in the morning, no evening dose; WEEK 2) 1 tablet PO twice daily in the morning and evening; WEEK 3) 2 tablets PO in the morning, 1 tablet PO in the evening; WEEK 4 AND ONWARD) 2 tablets PO twice daily in the morning and evening. Max daily dose: 32 mg/360 mg per day (2 tablets PO twice daily). Evaluate response after 12 weeks at the maintenance dosage. If the patient has not lost at least 5% of baseline body weight, discontinue, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.[57922] INTENDED USE: As an adjunct to lifestyle therapy for chronic weight management in adults with an initial body mass index (BMI) of at least 30 kg/m2 or a BMI of at least 27 kg/m2 in the presence of at least 1 weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes). The effect of therapy on cardiovascular morbidity and mortality has not been established. Do not give with other bupropion products. Safety and efficacy in combination with other products intended for weight loss, including prescription and non-prescription drugs, dietary supplements, and herbal preparations have not been established.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, pharmacotherapy should be offered as chronic treatment along with lifestyle modifications to obese patients when the potential benefits outweigh the risks. Short-term pharmacotherapy has not been shown to produce longer-term health benefits and cannot be generally recommended. A generalized hierarchy for medication preferences that would apply to all obese patients cannot currently be scientifically justified. Individualized weight loss pharmacotherapy is recommended, based on factors such as the specific characteristics of each weight loss medication, the presence of weight-related complications, and the medical history of the patient. Combination therapy with weight loss medications should only occur when such therapy is approved by the governing agency or when sufficient safety and efficacy data assure a favorable benefit-to-risk ratio.[62881]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults <p>32 mg naltrexone/360 mg bupropion PO daily.</p>
    • Geriatric <p>32 mg naltrexone/360 mg bupropion PO daily; use with caution.</p>
    • Adolescents <p>Safety and efficacy have not been established.</p>
    • Children <p>Safety and efficacy have not been established.</p>
    • Infants <p>Safety and efficacy have not been established.</p>
    • Neonates <p>Safety and efficacy have not been established.</p>

    Patients with Hepatic Impairment Dosing

    Mild hepatic impairment (Child-Pugh class A): No dosage adjustments needed.

    Moderate hepatic impairment (Child-Pugh class B): The maximum recommended maintenance dose is 1 tablet (8-mg naltrexone with 90-mg bupropion) PO twice daily, given each morning and evening.

    Severe hepatic impairment (Child-Pugh class C): Avoid use.[57922]

    Patients with Renal Impairment Dosing

    Mild renal impairment (i.e., CrCL 50 to 80 mL/minute): No dosage adjustment is needed. Adjust to clinical tolerability.

    Moderate or Severe renal impairment (i.e., CrCl 15 to 49 mL/minute): The maximum recommended maintenance dose is 1 tablet (8-mg naltrexone with 90-mg bupropion) PO twice daily, given each morning and evening. Guidelines recommend against use if CrCl is less than 30 mL/minute.[57922] [62881]

    End-stage renal disease (ESRD); ESRD on dialysis (i.e., CrCl less than 15 mL/minute): Use not recommended due to significantly increased exposure to the individual product components.[57922] [62881]

     

    Intermittent hemodialysis:

    Use not recommended due to significantly increased exposure to the individual product components.[57922] [62881]

    † Off-label indication
    Revision Date: 08/07/2020, 03:03:41 PM

    References

    57922 - Contrave (naltrexone HCl and bupropion HCl) extended-release tablets package insert. La Jolla, CA: Nalpropion Pharmaceuticals, Inc.; 2020 Aug.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22 Suppl 3:1-203.

    How Supplied

    Naltrexone Hydrochloride, Bupropion Hydrochloride Oral tablet, extended release

    Contrave 8mg-90mg Extended-Release Tablet (51267-0890) (Currax Pharmaceuticals, LLC) (off market)

    Naltrexone Hydrochloride, Bupropion Hydrochloride Oral tablet, extended release

    Contrave 8mg-90mg Extended-Release Tablet (51267-0890) (Currax Pharmaceuticals, LLC) null

    Naltrexone Hydrochloride, Bupropion Hydrochloride Oral tablet, extended release

    Contrave 8mg-90mg Extended-Release Tablet (51267-0890) (Nalpropion Pharmaceuticals, Inc.) (off market)

    Naltrexone Hydrochloride, Bupropion Hydrochloride Oral tablet, extended release

    Contrave 8mg-90mg Extended-Release Tablet (51267-0890) (Orexigen Therapeutics Inc.) (off market)

    Naltrexone Hydrochloride, Bupropion Hydrochloride Oral tablet, extended release

    Contrave 8mg-90mg Extended-Release Tablet (64764-0890) (Orexigen Therapeutics Inc.) (off market)

    Naltrexone Hydrochloride, Bupropion Hydrochloride Oral tablet, extended release

    Contrave 8mg-90mg Extended-Release Tablet (43063-0772) (PD-Rx Pharmaceuticals, Inc.) null

    Naltrexone Hydrochloride, Bupropion Hydrochloride Oral tablet, extended release

    Contrave 8mg-90mg Extended-Release Tablet (64764-0890) (Takeda Pharmaceuticals North America Inc) (off market)

    Description/Classification

    Description

    Bupropion; naltrexone is a combination product containing an antidepressant (bupropion) and an opioid antagonist (naltrexone). The combination is used as an adjunct to lifestyle modifications for weight loss and chronic weight management in obese adults, or in overweight adults with at least 1 weight-related comorbidity (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia).[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications should be offered as chronic treatment along with lifestyle modifications to obese patients when the potential benefits outweigh the risks. Short-term pharmacotherapy has not been shown to produce longer-term health benefits and cannot be generally recommended. A generalized hierarchy for medication preferences that would apply to all obese patients cannot currently be scientifically justified. Individualized weight loss pharmacotherapy is recommended, based on factors such as the specific characteristics of each weight loss medication, the presence of weight-related complications, and the medical history of the patient.[62881] Due to the risk for seizure, patients must not take other bupropion products concurrently. The boxed warning in the label also alerts to risks for depression, suicidal thoughts, and potential for neuropsychiatric events.[57922] Bupropion; naltrexone was FDA-approved in 2014.

    Classifications

    • Alimentary Tract and Metabolism
      • Antiobesity Agents, Excluding Dietetics
        • Other Antiobesity Agents
    Revision Date: 12/28/2018, 06:30:07 PM

    References

    57922 - Contrave (naltrexone HCl and bupropion HCl) extended-release tablets package insert. La Jolla, CA: Nalpropion Pharmaceuticals, Inc.; 2020 Aug.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22 Suppl 3:1-203.

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

    Route-Specific Administration

    Oral Administration

    Oral Solid Formulations

    Extended-release tablets (e.g., Contrave)

    • Do not cut, chew, or crush.
    • Administer by mouth in the morning and in the evening.
    • May be administered with or without food; avoid administering with high-fat meals due to significant increases in bupropion and naltrexone systemic exposure.[57922]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
      Revision Date: 01/01/2019, 01:38:49 PM

      References

      57922 - Contrave (naltrexone HCl and bupropion HCl) extended-release tablets package insert. La Jolla, CA: Nalpropion Pharmaceuticals, Inc.; 2020 Aug.

      Adverse Reactions

      Moderate

      • amnesia
      • constipation
      • dehydration
      • dyspnea
      • elevated hepatic enzymes
      • hallucinations
      • hepatitis
      • hostility
      • hot flashes
      • hypertension
      • impotence (erectile dysfunction)
      • mania
      • memory impairment
      • palpitations
      • psychosis
      • sinus tachycardia
      • vaginal bleeding

      Mild

      • abdominal pain
      • agitation
      • alopecia
      • anxiety
      • arthralgia
      • diarrhea
      • dizziness
      • dysgeusia
      • emotional lability
      • eructation
      • fatigue
      • fever
      • headache
      • hyperhidrosis
      • infection
      • influenza
      • insomnia
      • irritability
      • lethargy
      • malaise
      • menstrual irregularity
      • muscle cramps
      • myalgia
      • nausea
      • paranoia
      • polydipsia
      • pruritus
      • rash
      • syncope
      • tinnitus
      • tremor
      • urinary urgency
      • urticaria
      • vertigo
      • vomiting
      • xerostomia

      Severe

      • anaphylactic shock
      • anaphylactoid reactions
      • angioedema
      • cholecystitis
      • erythema multiforme
      • myocardial infarction
      • ocular hypertension
      • seizures
      • serum sickness
      • Stevens-Johnson syndrome
      • suicidal ideation

      Bupropion; naltrexone can cause an increase in systolic and/or diastolic blood pressure as well as an increase in resting heart rate. Therefore, avoid using bupropion; naltrexone in patients with uncontrolled hypertension. Measure blood pressure and pulse prior to and at regular intervals during bupropion; naltrexone therapy, particularly among patients with controlled hypertension prior to treatment. Monitor closely during titration and the initial three months of therapy when the risk is greatest. In bupropion; naltrexone clinical trails, statistically significant increases in blood pressure and heart rate were observed in patients with and without preexisting hypertension. The clinical significance of these findings are unclear, especially in patiens with cardiovascular disease, since patients with a history of cardiac and cerebrovascular events were excluded from bupropion; naltrexone clinical trials. In clinical practice with other bupropion-containing products, hypertension, in some cases severe and requiring acute treatment, has been reported. The overall safety of bupropion; naltrexone was evaluated in 5 double-blind placebo controlled clinical trials enrolling overweight (n = 4,754) or obese patients (n = 3,239) for up to 56 weeks of treatment. All subjects received study drug in addition to diet and exercise counseling. The majority of participants received a total daily dose of 32 mg naltrexone/360 mg bupropion. Common cardiovascular adverse reactions reported in 2% or more of patients receiving bupropion; naltrexone and more frequently than placebo include: hypertension (2.4% to 3.2%) and palpitations (2.1%). Other cardiovascular related adverse reactions reported in less than 2% of patients treated with bupropion; naltrexone but with an incidence at least twice that of placebo include: sinus tachycardia and myocardial infarction.[57922]

      Although not reported during clinical evaluation of bupropion; naltrexone, ocular hypertension has been reported during bupropion treatment.[40993] The pupillary dilation that occurs following the use of many antidepressant drugs including bupropion, may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.[57922]

      The overall safety of bupropion; naltrexone was evaluated in 5 double-blind placebo controlled clinical trials enrolling overweight (n = 4,754) or obese patients (n = 3,239) for up to 56 weeks of treatment. All subjects received study drug in addition to diet and exercise counseling. The majority of participants received a total daily dose of 32 mg naltrexone/360 mg bupropion. During clinical trials, headache was among the most frequent adverse reactions leading to discontinuation. Dizziness was also reported to account for a number of discontinuations of treatment in clinical trials. Adverse reactions involving attention, dizziness, and syncope occurred more often in individuals randomized to bupropion; naltrexone compared to placebo (15%). Common neurological adverse reactions reported in at least 2% of patients receiving bupropion; naltrexone and more frequently than placebo included headache (17.6%), dizziness (9.9%), tremor (4%), and tinnitus (3.3%). Other neurological related adverse reactions reported in less than 2% of patients treated with bupropion; naltrexone but with an incidence at least twice that of placebo include: amnesia, balance disorder, disturbance in attention, intention tremor, lethargy, memory impairment, mental impairment, motion sickness, presyncope, and vertigo. Loss of consciousness has been reported during postmarketing use; however, frequency and causality have not been established.[57922]

      Anaphylactoid reactions characterized by symptoms such as pruritus, urticaria, angioedema, and dyspnea requiring medical treatment have been reported in clinical trials with bupropion. In addition, there have been rare spontaneous post-marketing reports of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock associated with bupropion. Instruct patients to discontinue bupropion; naltrexone and consult a healthcare provider if they develop an allergic or anaphylactoid/anaphylactic reaction (e.g., skin rash, pruritus, hives, chest pain, edema, or shortness of breath) during treatment. Arthralgia, myalgia, fever with rash, and other symptoms suggestive of delayed hypersensitivity have been reported in association with bupropion. These symptoms may resemble serum sickness.[57922] The overall safety of bupropion; naltrexone was evaluated in 5 double-blind placebo controlled clinical trials enrolling overweight (n = 4,754) or obese patients (n = 3,239) for up to 56 weeks of treatment. All subjects received study drug in addition to diet and exercise counseling. The majority of participants received a total daily dose of 32 mg naltrexone/360 mg bupropion. Common dermatological adverse reactions reported in 2% or more of patients receiving bupropion; naltrexone and more frequently than placebo include: hyperhidrosis (2.6%) and rash (unspecified) (2.4%). Other skin related adverse reactions reported in less than 2% of patients treated with bupropion; naltrexone but with an incidence at least twice that of placebo include: alopecia.[57922]

      The overall safety of bupropion; naltrexone was evaluated in 5 double-blind placebo controlled clinical trials enrolling overweight (n = 4,754) or obese patients (n = 3,239) for up to 56 weeks of treatment. All subjects received study drug in addition to diet and exercise counseling. The majority of participants received a total daily dose of 32 mg naltrexone/360 mg bupropion. Common phychiatric adverse reactions reported in 2% or more of patients receiving bupropion; naltrexone and more frequently than placebo include: insomnia (9.2%), anxiety (4.2%), and irritability (2.6%). Other phychiatric related adverse reactions reported in less than 2% of patients treated with bupropion; naltrexone but with an incidence at least twice that of placebo include: abnormal dreams, nervousness, dissociation (feeling spacey), tension, agitation, emotional lability. Of note, in a one-year controlled trial, patients 65 years of age and older experienced more psychiatric and sleep disorder adverse reactions in the treatment group (28.6%, n = 56) compared to placebo (6.3%, n = 32); the majority of these events were insomnia and depression.[57922] Observe patients receiving bupropion; naltrexone for the occurrence of neuropsychiatric reactions and suicidal ideation. Bupropion, when prescribed as an antidepressant or as an aid in smoking cessation, has been associated with an increased incidence of neuropsychiatric reactions including suicidal thoughts and behaviors. Antidepressant treatment can precipitate a manic, mixed, or hypomanic episode. The risk appears to be increased in patients with bipolar disorder or who have risk factors for bipolar disorder. No activation of mania or hypomania was reported in the clinical trials evaluating effects of bupropion; naltrexone in obese patients; however, patients receiving antidepressant medications and patients with a history of bipolar disorder or recent hospitalization because of psychiatric illness were excluded from bupropion; naltrexone clinical trials. When bupropion is used in smoking cessation treatment, serious neuropsychiatric symptoms including changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide have been reported. Although bupropion; naltrexone is not approved for these indications, screen patients for a history of bipolar disorder and the presence of risk factors for bipolar disorder (e.g., family history of bipolar disorder, suicide, or depression) prior to initiating weight-loss therapy. Instruct patients and caregivers to contact a healthcare professional if neuropsychiatric reactions occur.[57922]

      The safety of bupropion; naltrexone was evaluated in 5 double-blind placebo controlled clinical trials enrolling overweight (n = 4,754) or obese patients (n = 3,239) for up to 56 weeks of treatment. All subjects received study drug in addition to diet and exercise counseling. The majority of participants received a total daily dose of 32 mg naltrexone/360 mg bupropion. During clinical trials, the most frequent adverse reactions leading to discontinuation included nausea and vomiting. Common gastrointestinal adverse reactions reported in 2% or more of patients receiving bupropion; naltrexone and more frequently than placebo include: nausea (32.5%), constipation (19.2%), vomiting (10.7%), xerostomia (8.1%), diarrhea (7.1%), upper abdominal pain (3.5%), viral gastroenteritis (3.5%), abdominal pain (2.8%), and dysgeusia (2.4%). Other GI related adverse reactions reported in less than 2% of patients treated with bupropion; naltrexone but with an incidence at least twice that of placebo include: lower abdominal pain, eructation, lip swelling, hematochezia, hernia, and cholecystitis.[57922]

      The safety of bupropion; naltrexone was evaluated in 5 double-blind placebo controlled clinical trials enrolling overweight (n = 4,754) or obese patients (n = 3,239) for up to 56 weeks of treatment. All subjects received study drug in addition to diet and exercise counseling. The majority of participants received a total daily dose of 32 mg naltrexone/360 mg bupropion. Common adverse reactions reported in 2% or more of patients receiving bupropion; naltrexone and more frequently than placebo include: hot flashes (4.2%), fatigue (4%), influenza (3.4%), urinary tract infection (3.3%), and muscle cramps / strains (2.2%). Other adverse reactions reported in less than 2% of patients treated with bupropion; naltrexone but with an incidence at least twice that of placebo include: asthenia, decreased hematocrit, dehydration, feeling abnormal, feeling hot, feeling jittery, impotence (erectile dysfunction), increased blood creatinine, intervertebral disc protrusion, jaw pain, kidney infection, menstrual irregularity, polydipsia, pneumonia, staphylococcal infection, urinary urgency, vaginal bleeding, and vulvovaginal dryness.[57922] In addition, in one-year controlled trials of bupropion; naltrexone, larger mean increases in serum creatinine from baseline to trial endpoint were observed in the treatment group compared with the placebo group. Malaise has been reported during postmarketing use; however, frequency and causality have not been established.[57922]

      Although not reported during clinical evaluation of bupropion; naltrexone, cases of hepatitis and clinically significant liver dysfunction were observed in association with naltrexone exposure during naltrexone clinical trials and in post-marketing reports for patients using naltrexone. Warn patients of the risk of hepatic injury and advised them to seek medical attention if they experience symptoms of acute hepatitis. Discontinue treatment with bupropion; naltrexone in the event of symptoms and/or signs of acute hepatitis. Transient, asymptomatic hepatic transaminase elevations have also been observed with naltrexone use; however, cases were often reported in patients with other potential contributory factors. In bupropion; naltrexone clinical trials, there were no cases of elevated transaminases greater than three times the upper limit of normal (ULN) in conjunction with an increase in bilirubin greater than two times ULN. Elevated hepatic enzymes were reported among less than 2% of bupropion; naltrexone treated patients but with an incidence at least twice that of placebo.[57922]

      Bupropion, a component of bupropion; naltrexone, is known to cause seizures in a dose dependent fashion. Avoid use of bupropion; naltrexone in patients at high risk for seizures and follow dosing recommendations closely in order to minimize the risk of bupropion induced seizures. If a patient experiences a seizure while on treatment, discontinue bupropion; naltrexone and do not restart. In clinical evaluation of bupropion; naltrexone, seizure was reported in 0.1% and 0% of patients receiving bupropion; naltrexone and placebo, respectively. Bupropion may cause amphetamine-like effects and therefore has been studied in patients with a history of substance abuse. Results from single-dose studies suggest that the recommended daily dose of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers. However, because clinical trial results may not reliably predict the abuse potential of drugs, the benefits of treatment should be weighed against the potential for abuse prior to administering bupropion; naltrexone to patients with a history of substance abuse. The inhalation of crushed bupropion tablets or injection of dissolved bupropion has resulted in seizures and/or cases of death.[57922]

      Revision Date: 02/25/2018, 05:36:23 PM

      References

      40993 - Wellbutrin SR (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.57922 - Contrave (naltrexone HCl and bupropion HCl) extended-release tablets package insert. La Jolla, CA: Nalpropion Pharmaceuticals, Inc.; 2020 Aug.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • acute opioid withdrawal
      • anorexia nervosa
      • bulimia nervosa
      • MAOI therapy
      • seizure disorder
      • seizures
      • abrupt discontinuation
      • alcoholism
      • arteriovenous malformation
      • bariatric surgery
      • behavioral changes
      • benzodiazepine withdrawal
      • bipolar disorder
      • brain tumor
      • breast-feeding
      • cardiac arrhythmias
      • cardiac disease
      • cerebrovascular disease
      • children
      • closed-angle glaucoma
      • contraception requirements
      • depression
      • diabetes mellitus
      • dialysis
      • geriatric
      • head trauma
      • heart failure
      • hepatic disease
      • hepatitis
      • hepatotoxicity
      • hypertension
      • hypoglycemia
      • hyponatremia
      • hypoxemia
      • infants
      • laboratory test interference
      • mania
      • myocardial infarction
      • neonates
      • pregnancy
      • psychiatric event
      • renal failure
      • renal impairment
      • schizophrenia
      • stroke
      • substance abuse
      • suicidal ideation

      Bupropion; naltrexone is contraindicated in patients with a history of hypersensitivity to bupropion, naltrexone or any inactive ingredients in the formulation. Delayed hypersensitivity reactions, consisting of arthralgia, myalgia, fever and rash have been reported in association with bupropion and may resemble serum sickness. Anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have also been reported.[57922]

       

      The use of bupropion; naltrexone is contraindicated with the concurrent use of other bupropion-containing products (including, but not limited to, brand names such as WELLBUTRIN, WELLBUTRIN SR, WELLBUTRIN XL, APLENZIN, ZYBAN and generic bupropion products).[57922]

      The concurrent administration of monoamine oxidase inhibitor therapy (MAOI therapy) during bupropion; naltrexone is contraindicated. At least 14 days should elapse between the discontinuation of an MAOI and initiation of bupropion; naltrexone treatment. Conversely, at least 14 days should be allowed after stopping bupropion; naltrexone before starting an MAOI.[57922] There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism such as MAOIs. Starting bupropion; naltrexone in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is also contraindicated. Clinicians are advised to carefully review the potential for drug-drug interactions prior to prescribing bupropion; naltrexone.[57922]

      Bupropion; naltrexone is contraindicated for use in patients with uncontrolled hypertension; use this product cautiously in patients with controlled hypertension. Bupropion; naltrexone is known to cause an increase in systolic and diastolic blood pressure as well as an increase in resting heart rate. Hypertension, in some cases severe and requiring acute treatment, has been reported with bupropion therapy for various indications in clinical practice. Monitor blood pressure and pulse before and at regular intervals during therapy, particularly among patients with controlled hypertension before treatment. Monitor closely during titration and the initial 3 months of therapy when the risk is highest.[57922] Use with caution and with appropriate monitoring of blood pressure, heart rate, and rhythm in patients with existing cardiac disease or cerebrovascular disease. Patients with cardiac disease or cerebrovascular disease, including patients with a history of acute myocardial infarction, myocardial infarction (MI) or cerebrovascular accident (CVA) in the previous 6 months, life-threatening cardiac arrhythmias, or heart failure were excluded from bupropion; naltrexone clinical trials and, thus, should only receive this product for weight management with careful consideration of risks and benefits and close monitoring.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, avoid bupropion; naltrexone in obese patients with existing hypertension if other weight loss medications are appropriate because weight loss assisted by bupropion; naltrexone cannot be expected to reduce blood pressure, and the product is contraindicated in uncontrolled hypertension. Bupropion; naltrexone is not a preferred weight loss medication in patients with established coronary artery disease (CAD) or history or risk of cardiac arrhythmias, but is reasonable to use with caution if weight loss goals are met, with careful monitoring of blood pressure, heart rate, and rhythm. Data are insufficient regarding the benefits of the use of bupropion; naltrexone in obese patients with heart failure; the AACE/ACE Obesity Guidelines recommend avoidance until more data are available.[62881]

      Bupropion; naltrexone use is contraindicated in patients with a seizure disorder, a history of seizures, and in patients undergoing abrupt benzodiazepine withdrawal, as well as abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs because the seizure risk is increased. Bupropion, a component of bupropion; naltrexone, is known to cause seizures in a dose-dependent fashion. Consider any other patient factors, clinical situations, and concomitant medications that may lower the seizure threshold before initiating treatment with bupropion; naltrexone. In particular, use bupropion; naltrexone with caution in patients with a history of head trauma, severe stroke, arteriovenous malformation, central nervous system (CNS) tumor (brain tumor) or CNS infection (e.g., meningitis), metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxemia), substance abuse (e.g., alcoholism or excessive use of alcohol or sedatives), addiction to cocaine or stimulants, or withdrawal from sedatives), patients with diabetes treated with insulin and/or oral diabetic medications (sulfonylureas and meglitinides) that may cause hypoglycemia, and during concomitant administration of medications that may lower the seizure threshold, including other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, or systemic steroids.[57922] Clinical experience suggests that the risk of seizures may be minimized by adhering to the dosing recommendations set forth for bupropion; naltrexone, including the following: a maximum daily bupropion dose of 360 mg/day (i.e., four tablets/day), administering the total daily dose in divided doses (twice daily), gradually titrating dose, taking no more than 2 tablets at any one time, avoiding administration with high-fat meals, and if a dose is missed, advising the patient to wait until the next scheduled dose to resume the regular dosing schedule. If a patient experiences a seizure while undergoing weight loss treatment with bupropion; naltrexone, discontinue therapy and do not restart.[57922] Bupropion may cause amphetamine-like effects and therefore has been studied in patients with a history of substance abuse. Results from single-dose studies suggest that the recommended daily dose of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers. Bupropion; naltrexone has not been formally studied for abuse potential, tolerance, or physical dependence. In outpatient clinical studies of up to 56 weeks, there was no evidence of euphoria, physical dependence, diversion, or abuse, or an abstinence syndrome following either abrupt or tapered drug discontinuation. Naltrexone is a pure opiate antagonist and does not lead to physical or psychological dependence. Weigh the benefits of obesity treatment against the potential for abuse before using bupropion; naltrexone in those with a history of substance abuse. Bupropion; naltrexone extended-release tablets are intended for oral use only; the inhalation of crushed bupropion tablets or injection of dissolved bupropion has resulted in seizures and cases of death.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, bupropion; naltrexone should be avoided in obese patients with alcoholism or substance abuse due to the seizure risk with bupropion which may increase the likelihood of seizures during alcohol or other medication withdrawal. The AACE/ACE Obesity Guidelines recommend that other weight loss medications be considered in patients with a substance abuse disorder.[62881]

      Bupropion; naltrexone use is contraindicated in patients with a current diagnosis or previous history of bulimia nervosa or anorexia nervosa because the risk for seizure is known to be increased in these patients.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, bupropion; naltrexone should be avoided in patients with eating disorders that involve purging or bulimia nervosa. Patients with bulimia may be susceptible to seizures due to metabolic imbalance or other risk factors. There are insufficient data on the use of bupropion; naltrexone in overweight or obese patients with binge eating disorder (BED), but there is a possible benefit based on studies with bupropion. According to the AACE/ACE Obesity Guidelines, there are insufficient data on the benefits of the use of bupropion; naltrexone following bariatric surgery.[62881]

      Bupropion; naltrexone contains naltrexone, an opioid receptor antagonist. Bupropion; naltrexone is contraindicated in patients who require chronic opioid therapy, in patients experiencing acute opioid withdrawal, and in patients receiving an opiate agonist (e.g., methadone, tramadol, and many others) or partial agonist (e.g., buprenorphine). If chronic opioid therapy is required, bupropion; naltrexone treatment should be stopped. To prevent the occurrence of either precipitated opioid withdrawal or exacerbation of pre-existing subclinical withdrawal symptoms, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free before starting bupropion; naltrexone treatment.[57922] An opioid-free interval of a minimum of 7 to 10 days is recommended for patients previously dependent on short-acting opioids; patients transitioning from buprenorphine or methadone may need as long as 2 weeks. Patients should be made aware of the risks associated with precipitated opioid withdrawal and encouraged to give an accurate account of last opioid use. In patients requiring intermittent opioid treatment, bupropion; naltrexone therapy should be temporarily discontinued, and lower doses of opioids may be needed. Even at lower opioid doses, patients may still experience increased sensitivity to opioid actions and adverse effects after bupropion; naltrexone treatment is discontinued. Advise patients of the serious consequences of trying to overcome the opioid blockade which may lead to a fatal overdose or life-threatening opioid intoxication (e.g., respiratory arrest, circulatory collapse).[57922]

      Bupropion; naltrexone therapy for weight management has not been studied in clinical trials and is not recommended in children and adolescents less than 18 years old; safety and efficacy have not been established.[57922] Use of agents for weight loss off-label in properly selected older children or adolescents is recommended to be within the context of appropriate clinical trials.[58571] The bupropion component of bupropion; naltrexone is used for the treatment of major depressive disorder (MDD) and smoking cessation; therefore, precautions about these bupropion products should be considered when treating patients with bupropion; naltrexone. All patients being treated with an antidepressant for any indication should be monitored and observed for the emergence of anxiety, agitation, irritability, unusual changes in behavior, or suicidality, and to report such symptoms immediately to healthcare providers. All antidepressants include a boxed warning detailing the risk of suicide in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n = 4,400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive-compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants. Pooled analysis of short-term clinical trials during early phase treatment with antidepressants in young adults (18 to 24 years) also showed an increased risk of suicidal thinking and behavioral changes. No suicides occurred in any of the pediatric antidepressant trials. It is unknown if the suicidality risk in children and young adults extends to longer-term therapy. In placebo-controlled trials with bupropion; naltrexone (equivalent to bupropion doses of 360 mg/day) for the treatment of obesity in adults, no suicides or suicide attempts were reported in studies up to 56 weeks duration. In these same studies, suicidal ideation was reported in 0.2% of patients treated with placebo compared with 0.03% of those treated with bupropion; naltrexone. Bupropion; naltrexone should be prescribed in the smallest quantity consistent with good patient management to reduce the risk of overdose.[57922]

      Serious neuropsychiatric adverse events have been reported in patients taking bupropion for various indications. Patients should be observed for a potential psychiatric event or worsening of pre-existing psychiatric illness (e.g., schizophrenia, depression, bipolar disorder) during treatment with bupropion; naltrexone. Antidepressants have been associated with the development of mania or hypomania in susceptible individuals, such as those with bipolar disorder or who have risk factors for bipolar disorder. Patients should be adequately screened for bipolar disorder and risk factors for bipolar disorder before initiating bupropion; naltrexone. No activation of mania or hypomania was reported in the clinical trials evaluating the effects of bupropion; naltrexone in obese patients; however, patients receiving other antidepressants or with a history of bipolar disorder or recent hospitalization because of psychiatric illness were excluded from the bupropion; naltrexone clinical weight loss trials. Postmarketing reports during use of bupropion products have included mood or behavioral changes (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempt, and completed suicide in patients with and without a psychiatric history. Advise patients and caregivers that the patient should stop taking bupropion; naltrexone and contact a healthcare provider immediately if agitation, depressed mood, suicidal ideation, suicidal behavior, or other behavioral changes that are not typical for the patient are observed. Depression, suicide, attempted suicide, and suicidal ideation has been reported during postmarketing use of naltrexone in the treatment of opioid dependence, although no causal relationship has been observed.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, there are insufficient safety data on the use of bupropion; naltrexone in obese patients with depression or other mood disorders. Use with caution and avoid bupropion; naltrexone in adolescents and young adults and those patients taking medication for depression. All patients undergoing weight loss therapy should be monitored for mood disorders, depression, and suicidal ideation. Evidence assessing safety and efficacy of weight loss medications in patients with a psychotic disorder (e.g., schizophrenia) is insufficient, and use of bupropion; naltrexone should be avoided. The AACE/ACE Obesity Clinical Guidelines suggest that patients receiving an antipsychotic be treated with structured lifestyle modifications to promote weight loss and weight gain prevention; metformin may be beneficial for modest weight loss and metabolic improvements in patients receiving an antipsychotic.[62881]

      Maximum recommended daily maintenance doses of bupropion; naltrexone are reduced in patients with moderate hepatic disease. Avoid use of this product in patients with severe hepatic disease. In a pharmacokinetic study of bupropion; naltrexone in subjects with hepatic impairment (mild, moderate, and severe) compared to normal controls, exposures to naltrexone, bupropion, and their metabolites were increased. Naltrexone as a single agent has been associated with transient, asymptomatic hepatic transaminase elevations as well as cases of hepatotoxicity, hepatitis, and other forms of significant liver dysfunction, although potential causative or contributory etiologies have often been identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other potentially hepatotoxic drugs. Warn patients of the risk of hepatic injury and advise them to seek medical attention if they experience symptoms of acute hepatitis. Discontinue treatment in the event of symptoms and/or signs of acute hepatitis. Close monitoring for cholelithiasis or pancreatitis is recommended in all obese patients, regardless of treatment, due to a proven association between obesity and these conditions.[57922] [62881]

      Caution is recommended when prescribing bupropion; naltrexone to patients with closed-angle glaucoma. The pupillary dilation that can occur with antidepressants may precipitate a closed-angle glaucoma attack in patients with anatomically narrow angles who do not have a patent iridectomy. An acute attack of closed-angle glaucoma is considered a medical emergency because the increased intraocular pressure is rapid and severe, and may quickly result in blindness if left untreated.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, other weight loss medications (i.e., orlistat, lorcaserin, or liraglutide) are preferred treatment options for patients with glaucoma and bupropion; naltrexone should be avoided if possible since the drug may trigger an acute attack of closed-angle glaucoma.[62881]

      Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus (T2DM) treated with insulin and/or insulin secretagogues (e.g., sulfonylureas). Monitor blood glucose levels before starting bupropion; naltrexone and during treatment. Decreases in medication doses for antidiabetic medications which are non-glucose-dependent should be considered to mitigate the risk of hypoglycemia. If a patient develops hypoglycemia after starting bupropion; naltrexone, appropriate changes should be made to the antidiabetic drug regimen. If a patient develops hypoglycemia after starting bupropion; naltrexone, appropriate changes should be made to the antidiabetic drug regimen.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications should be considered as an adjunct to lifestyle therapy in all patients with T2DM as needed for weight loss sufficient to improve glycemic control, lipids, and blood pressure. There are insufficient data to determine if bupropion; naltrexone prevents progression to T2DM in obese patients. In controlled trials of other prescribed weight loss medications (i.e., orlistat, phentermine; topiramate, or liraglutide) as an adjunct to lifestyle therapy versus lifestyle therapy alone for diabetes prevention, a greater weight loss and more profound reductions in incident diabetes occurred in the medication plus lifestyle therapy groups[62881]

      No dosage adjustments of bupropion; naltrexone are required in patients with mild renal impairment. Due to an increase in exposure of naltrexone and metabolites of bupropion, maximum dosages of bupropion; naltrexone are recommended to be reduced in patients with moderate to severe renal impairment. Bupropion; naltrexone is not recommended for use in patients with end-stage renal disease (i.e., renal failure or ESRD on dialysis).[57922] The American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines state to avoid this product in patients with a CrCl less than 30 mL/minute. Bupropion; naltrexone is a preferred weight loss medication in patients with a history of or at risk for nephrolithiasis, as this product does not increase the risk for renal stones.[62881]

      Use caution when prescribing bupropion; naltrexone to geriatric patients. Clinical studies for obesity did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects; no patients in clinical trials were over the age of 75 years. Older patients may be more sensitive to the central nervous system (CNS) adverse effects of bupropion; naltrexone. The drug components are renally excreted and the risk of adverse reactions are greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, there are insufficient data on the use of bupropion; naltrexone for weight reduction in elderly obese patients and additional studies are needed to assess safety and efficacy. Elderly patients selected for weight loss therapy should have structured lifestyle interventions including reduced calorie meal plans and exercise, clear health-related goals including blood pressure reduction, diabetes prevention in high risk patients with pre-diabetes, and improvements in osteoarthritis, mobility, and physical functioning. Overweight or obese elderly patients being considered for a weight loss medication should be evaluated for osteopenia and sarcopenia.[62881]

      Weight loss offers no benefit during pregnancy and may result in fetal harm; therefore, if pregnancy occurs during the use of bupropion; naltrexone, the patient should be apprised of the risk to the fetus and the drug should be discontinued. Available data from the individual components of bupropion; naltrexone use in pregnant patients have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, a minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese, due to the obligatory weight gain that occurs in maternal tissues during pregnancy. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications must not be used during pregnancy. The AACE/ACE Obesity Guidelines recommend contraception requirements. Women of childbearing potential receiving bupropion; naltrexone should use contraception and discontinue the drug if pregnancy occurs. There is no known indication for the use of obesity drugs in infants; the effect on infants or neonates exposed in utero is uncertain; drug-related withdrawal syndromes have been reported postpartum from the maternal use of antidepressant category drugs of other types during pregnancy.[57922] [62881]

      The developmental and health benefits of breast-feeding should be considered along with the clinical need for bupropion; naltrexone to the mother and any potential adverse effects on the breastfed infant from the drug or from the underlying condition of the mother. Bupropion and its metabolites are excreted in human milk. Transfer of naltrexone and 6-beta-naltrexol into human milk has been reported with oral naltrexone. There are no data on bupropion; naltrexone or their metabolites on milk production. In 1 small lactation study (n = 10) of bupropion, the average daily infant exposure (assuming 150 mL/kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. Postmarketing reports have described seizures in breastfed infants exposed to bupropion through breast milk; however, causality has not been established. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight-loss medications should not be used in women who are lactating and breast-feeding.[57922] [62881]

      Laboratory test interference has been reported with bupropion use. False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion. The false-positive result is due to lack of specificity of some screening tests. False-positive test results may result even following discontinuation of bupropion therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.[57922]

      Revision Date: 08/07/2020, 03:35:15 PM

      References

      57922 - Contrave (naltrexone HCl and bupropion HCl) extended-release tablets package insert. La Jolla, CA: Nalpropion Pharmaceuticals, Inc.; 2020 Aug.58571 - Styne DM, Arslanian SA, Connor EL, et al. Pediatric Obesity-Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102:709-757.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22 Suppl 3:1-203.

      Mechanism of Action

      Bupropion; naltrexone consists of naltrexone, an opioid antagonist, and bupropion, a relatively weak inhibitor of the neuronal reuptake of dopamine and norepinephrine. Nonclinical studies suggest that naltrexone and bupropion have effects on two separate areas of the brain involved in the regulation of food intake: the hypothalamus (appetite regulatory center) and the mesolimbic dopamine circuit (reward system). In vitro, bupropion; naltrexone increased the firing rate of hypothalamic proopiomelanocortin (POMC) neurons, which are associated with regulation of appetite. The combination also reduced food intake when injected directly into the ventral tegmental area of the mesolimbic circuit in mice, an area associated with regulation of reward pathways. The exact neurochemical effects of bupropion; naltrexone leading to weight loss are not fully understood.[57922]

       


       

      Revision Date: 09/23/2014, 05:59:47 PM

      References

      57922 - Contrave (naltrexone HCl and bupropion HCl) extended-release tablets package insert. La Jolla, CA: Nalpropion Pharmaceuticals, Inc.; 2020 Aug.

      Pharmacokinetics

      Bupropion; naltrexone tablets are administered orally.[57922]

      • Bupropion: Bupropion is 84% plasma protein bound. Bupropion is extensively metabolized to three active metabolites; hydroxybupropion, threohydrobupropion, and erythrohydrobupropion. Plasma protein binding of hydroxybupropion, the major metabolite, is similar to that of bupropion whereas the other two metabolites have approximately half the binding. The metabolites have longer elimination half lives than bupropion and accumulate to a greater extent. Following bupropion administration, more than 90% of the exposure is a result of metabolites. Following oral administration of 200 mg of radio labelled bupropion in humans, 87% and 10% of the radioactive dose were recovered in the urine and feces, respectively. The fraction of the oral dose of bupropion excreted unchanged was 0.5%, a finding consistent with the extensive metabolism of bupropion. Following single oral administration of bupropion; naltrexone tablets to healthy subjects, mean elimination half life was approximately 21 hours for bupropion. Following twice daily administration of bupropion; naltrexone, metabolites of bupropion, and to a lesser extent unchanged bupropion, accumulate and reach steady state concentrations in approximately one week.[57922]
      • Naltrexone: Naltrexone is 21% plasma protein bound. The major metabolite of naltrexone is 6 beta naltrexol. The activity of naltrexone is believed to be the result of both the parent and the 6 beta naltrexol metabolite. Though less potent, 6 beta naltrexol is eliminated more slowly and thus circulates at much higher concentrations than naltrexone. Naltrexone and its metabolites are excreted primarily by the kidney (53% to 79% of the dose). Urinary excretion of unchanged naltrexone accounts for less than 2% of an oral dose. Urinary excretion of unchanged and conjugated 6 beta naltrexol accounts for 43% of an oral dose. The renal clearance for naltrexone ranges from 30 to 127 mL/min, suggesting that renal elimination is primarily by glomerular filtration. The renal clearance for 6 beta naltrexol ranges from 230 to 369 ml/min suggesting an additional renal tubular secretory mechanism. Fecal excretion is a minor elimination pathway. Following single oral administration of bupropion; naltrexone tablets to healthy subjects, mean elimination half life was approximately 5 hours for naltrexone. Following twice daily administration of bupropion; naltrexone, naltrexone did not accumulate and its kinetics appeared linear. However, in comparison to naltrexone, 6 beta naltrexol accumulates to a larger extent (accumulation ratio approximately 3).[57922]

       

      Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6, CYP2B6, OCT2

      Extensive metabolism of bupropion occurs through CYP2B6, forming hydroxybupropion, the major metabolite. Because of the extensive metabolism of bupropion by CYP2B6, clinically significant drug interactions are possible with drugs that are metabolized by or are inhibitors or inducers of CYP2B6. Bupropion and its metabolites hydroxybupropion, threohydrobupropion, and erythrohydrobupropion are inhibitors of CYP2D6. In vitro, bupropion and its 3 metabolites are inhibitors of the renal organic transporter OCT2 to a clinically significant extent; however, in vivo drug interaction studies have not found clinically significant drug-drug interactions with OCT-2 substrates.[41086][57922] Naltrexone and 6 beta naltrexol are not metabolized by CYP isoenzymes and in vitro studies indicate that there is no potential for inhibition or induction of important isoenzymes.[57922]

      Route-Specific Pharmacokinetics

      Oral Route

      • Bupropion: Following single oral administration of bupropion; naltrexone (two 8 mg naltrexone/90 mg bupropion tablets) to healthy subjects, bupropion mean peak concentration (Cmax) was 168 ng/mL, time to peak concentration (Tmax) was 3 hours, and extent of exposure (AUC) was 1,607 ng x hour/mL. When administered with a high fat meal, the AUC and Cmax for bupropion increased 1.4 fold and 1.8 fold, respectively. At steady state, the food effect increased AUC and Cmax for bupropion by 1.1 fold and 1.3 fold, respectively. Avoid bupropion; naltrexone administration with high fat meals, due to significant increases in systemic exposure.[57922]
      • Naltrexone: Following single oral administration of bupropion; naltrexone (two 8 mg naltrexone/90 mg bupropion tablets) to healthy subjects, naltrexone Cmax was 1.4 ng/mL, Tmax was 2 hours, and AUC was 8.4 ng x hour/mL. When administered with a high fat meal, the AUC and Cmax for naltrexone increased 2.1 fold and 3.7 fold, respectively. At steady state, the food effect increased AUC and Cmax for naltrexone by 1.7 fold and 1.9 fold, respectively. Avoid bupropion; naltrexone administration with high fat meals, due to significant increases in systemic exposure.[57922]

      Special Populations

      Hepatic Impairment

      In a pharmacokinetic study of bupropion; naltrexone in subjects with hepatic impairment (mild, moderate, and severe) compared to normal controls, exposures to naltrexone, bupropion, and their metabolites were increased. Following a single dose of bupropion; naltrexone, the AUC of naltrexone was approximately 2.8-, 6.1-, and 34-fold higher in patients with mild, moderate, and severe hepatic impairment, respectively. In patients with moderate and severe hepatic impairment, the AUC of bupropion was approximately 2- and 3.6-fold higher, respectively, compared to subjects with normal hepatic function. There was no effect of mild hepatic impairment on bupropion exposure. Exposure to the bupropion metabolite threohydrobupropion was increased by 1.9-, 3.4-, and 2.5-fold in patients with mild, moderate, and severe hepatic impairment, respectively. The maximum recommended daily maintenance dose of bupropion; naltrexone should be reduced in patients with moderate hepatic disease. Bupropion; naltrexone is not recommended in patients with severe hepatic impairment.[57922]

      Renal Impairment

      In a single-dose pharmacokinetic study of bupropion; naltrexone 16 mg/180 mg in subjects with mild to severe renal impairment compared to subjects with normal renal function, the pharmacokinetics of the parent compounds bupropion and naltrexone were not significantly affected; however, the AUC of the naltrexone metabolite 6-beta naltrexol was increased 1.5, 1.7, and 2.2 in patients with mild, moderate, and severe renal impairment, respectively. In addition, the AUC of the bupropion metabolites were increased as follows in mild, moderate, and severe renal impairment, respectively: threohydrobupropion (1.3, 1.9, 1.7) and erythrohydrobupropion (1.2, 1.8, 1.5). Dosage adjustments are recommended in patients with moderate to severe impairment. No studies have been conducted with this product in patients with end-stage renal disease (ESRD) or ESRD on dialysis and use of the product is not recommended in these populations. As noted, studies with the individual components in patients with renal failure indicate that naltrexone exposure is significantly increased, and exposure to bupropion metabolites is also increased. An inter-trial comparison between normal subjects and patients with end-stage renal failure demonstrated that the bupropion Cmax and AUC values were comparable in the two groups, whereas the hydroxybupropion and threohydrobupropion metabolite AUCs increased 2.3 and 2.8-fold, respectively, in the patients with end-stage renal failure. In a study of seven patients with ESRD requiring dialysis, peak plasma concentrations of naltrexone were elevated at least 6-fold compared to healthy subjects.[57922]

      Geriatric

      The pharmacokinetics of bupropion; naltrexone have not been evaluated in the geriatric population. The effects of age on the pharmacokinetics of naltrexone or bupropion and their metabolites have not been fully characterized. An exploration of steady state bupropion concentrations from several depression efficacy studies involving patients dosed in a range of 300—750 mg/day, on a three times daily schedule, revealed no relationship between age (18—83 years) and plasma concentration of bupropion. A single-dose pharmacokinetic study demonstrated that the disposition of bupropion and its metabolites in elderly subjects was similar to that of younger subjects. These data suggest there is no prominent effect of age on bupropion concentration; however, another pharmacokinetic study, single and multiple dose, has suggested that the elderly are at increased risk for accumulation.[57922]

      Gender Differences

      Pooled analysis of bupropion; naltrexone data suggested no clinically meaningful differences in the pharmacokinetic parameters of bupropion or naltrexone based on gender.[57922]

      Ethnic Differences

      Pooled analysis of bupropion; naltrexone data suggested no clinically meaningful differences in the pharmacokinetic parameters of bupropion or naltrexone based on race.[57922]

      Other

      Pooled analysis of bupropion; naltrexone data revealed no meaningful differences in the plasma concentrations of bupropion or naltrexone in smokers compared with nonsmokers. [57922]

      Revision Date: 08/07/2020, 03:45:13 PM

      References

      41086 - Wellbutrin (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.57922 - Contrave (naltrexone HCl and bupropion HCl) extended-release tablets package insert. La Jolla, CA: Nalpropion Pharmaceuticals, Inc.; 2020 Aug.

      Pregnancy/Breast-feeding

      contraception requirements, infants, neonates, pregnancy

      Weight loss offers no benefit during pregnancy and may result in fetal harm; therefore, if pregnancy occurs during the use of bupropion; naltrexone, the patient should be apprised of the risk to the fetus and the drug should be discontinued. Available data from the individual components of bupropion; naltrexone use in pregnant patients have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, a minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese, due to the obligatory weight gain that occurs in maternal tissues during pregnancy. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications must not be used during pregnancy. The AACE/ACE Obesity Guidelines recommend contraception requirements. Women of childbearing potential receiving bupropion; naltrexone should use contraception and discontinue the drug if pregnancy occurs. There is no known indication for the use of obesity drugs in infants; the effect on infants or neonates exposed in utero is uncertain; drug-related withdrawal syndromes have been reported postpartum from the maternal use of antidepressant category drugs of other types during pregnancy.[57922] [62881]

      breast-feeding

      The developmental and health benefits of breast-feeding should be considered along with the clinical need for bupropion; naltrexone to the mother and any potential adverse effects on the breastfed infant from the drug or from the underlying condition of the mother. Bupropion and its metabolites are excreted in human milk. Transfer of naltrexone and 6-beta-naltrexol into human milk has been reported with oral naltrexone. There are no data on bupropion; naltrexone or their metabolites on milk production. In 1 small lactation study (n = 10) of bupropion, the average daily infant exposure (assuming 150 mL/kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. Postmarketing reports have described seizures in breastfed infants exposed to bupropion through breast milk; however, causality has not been established. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight-loss medications should not be used in women who are lactating and breast-feeding.[57922] [62881]

      Revision Date: 08/07/2020, 03:14:15 PM

      References

      57922 - Contrave (naltrexone HCl and bupropion HCl) extended-release tablets package insert. La Jolla, CA: Nalpropion Pharmaceuticals, Inc.; 2020 Aug.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22 Suppl 3:1-203.

      Interactions

      Level 1 (Severe)

      • Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
      • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
      • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
      • Isocarboxazid
      • Linezolid
      • Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine
      • Methylene Blue
      • Monoamine oxidase inhibitors
      • Ozanimod
      • Phenelzine
      • Pimozide
      • Procarbazine
      • Rasagiline
      • Selegiline
      • Thioridazine
      • Tranylcypromine

      Level 2 (Major)

      • Acetaminophen; Butalbital; Caffeine; Codeine
      • Acetaminophen; Caffeine; Dihydrocodeine
      • Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
      • Acetaminophen; Codeine
      • Acetaminophen; Dextromethorphan; Pseudoephedrine
      • Acetaminophen; Hydrocodone
      • Acetaminophen; Oxycodone
      • Acetaminophen; Pentazocine
      • Acetaminophen; Propoxyphene
      • Acetaminophen; Pseudoephedrine
      • Acetaminophen; Tramadol
      • Acrivastine; Pseudoephedrine
      • Alfentanil
      • Alvimopan
      • Amantadine
      • Amifampridine
      • Amitriptyline
      • Amitriptyline; Chlordiazepoxide
      • Amoxapine
      • Amphetamine
      • Amphetamine; Dextroamphetamine
      • Amphetamine; Dextroamphetamine Salts
      • Aripiprazole
      • Armodafinil
      • Asenapine
      • Aspirin, ASA; Butalbital; Caffeine; Codeine
      • Aspirin, ASA; Caffeine; Dihydrocodeine
      • Aspirin, ASA; Carisoprodol; Codeine
      • Aspirin, ASA; Oxycodone
      • Atomoxetine
      • Atropine; Difenoxin
      • Atropine; Diphenoxylate
      • Benzphetamine
      • Bremelanotide
      • Brexpiprazole
      • Brompheniramine; Guaifenesin; Hydrocodone
      • Brompheniramine; Hydrocodone; Pseudoephedrine
      • Brompheniramine; Pseudoephedrine
      • Buprenorphine
      • Buprenorphine; Naloxone
      • Butorphanol
      • Calcium, Magnesium, Potassium, Sodium Oxybates
      • Carbetapentane; Pseudoephedrine
      • Carbidopa; Levodopa
      • Carbidopa; Levodopa; Entacapone
      • Carbinoxamine; Dextromethorphan; Pseudoephedrine
      • Carbinoxamine; Hydrocodone; Phenylephrine
      • Carbinoxamine; Hydrocodone; Pseudoephedrine
      • Carbinoxamine; Pseudoephedrine
      • Cariprazine
      • Cenobamate
      • Cetirizine; Pseudoephedrine
      • Chlophedianol; Dexchlorpheniramine; Pseudoephedrine
      • Chlorpheniramine; Codeine
      • Chlorpheniramine; Dihydrocodeine; Phenylephrine
      • Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
      • Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
      • Chlorpheniramine; Hydrocodone
      • Chlorpheniramine; Hydrocodone; Phenylephrine
      • Chlorpheniramine; Hydrocodone; Pseudoephedrine
      • Chlorpheniramine; Pseudoephedrine
      • Chlorpromazine
      • Clomipramine
      • Clozapine
      • Cocaine
      • Codeine
      • Codeine; Guaifenesin
      • Codeine; Phenylephrine; Promethazine
      • Codeine; Promethazine
      • Cyclobenzaprine
      • Dabrafenib
      • Desipramine
      • Desloratadine; Pseudoephedrine
      • Deutetrabenazine
      • Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine
      • Dexmethylphenidate
      • Dextroamphetamine
      • Dextromethorphan; Guaifenesin; Pseudoephedrine
      • Dextromethorphan; Promethazine
      • Diethylpropion
      • Dihydrocodeine; Guaifenesin; Pseudoephedrine
      • Diphenhydramine; Hydrocodone; Phenylephrine
      • Disulfiram
      • Doxepin
      • Doxorubicin
      • Efavirenz
      • Efavirenz; Emtricitabine; Tenofovir
      • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
      • Encainide
      • Ethanol
      • Felbamate
      • Fentanyl
      • Fexofenadine; Pseudoephedrine
      • Flecainide
      • Fluoxetine; Olanzapine
      • Fluphenazine
      • Guaifenesin; Hydrocodone
      • Guaifenesin; Hydrocodone; Pseudoephedrine
      • Guaifenesin; Pseudoephedrine
      • Haloperidol
      • Homatropine; Hydrocodone
      • Hydrocodone
      • Hydrocodone; Ibuprofen
      • Hydrocodone; Phenylephrine
      • Hydrocodone; Potassium Guaiacolsulfonate
      • Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine
      • Hydrocodone; Pseudoephedrine
      • Hydromorphone
      • Ibuprofen; Oxycodone
      • Ibuprofen; Pseudoephedrine
      • Iloperidone
      • Imipramine
      • Iobenguane I 131
      • Levodopa
      • Levomethadyl
      • Levorphanol
      • Lisdexamfetamine
      • Lofexidine
      • Loratadine; Pseudoephedrine
      • Loxapine
      • Lurasidone
      • Maprotiline
      • Meperidine
      • Meperidine; Promethazine
      • Methadone
      • Methamphetamine
      • Methylnaltrexone
      • Methylphenidate
      • Metoclopramide
      • Mexiletine
      • Modafinil
      • Molindone
      • Morphine
      • Morphine; Naltrexone
      • Nalbuphine
      • Naldemedine
      • Naloxegol
      • Naproxen; Pseudoephedrine
      • Non-Ionic Contrast Media
      • Nortriptyline
      • Olanzapine
      • Opiate Agonists-Antagonists
      • Oxycodone
      • Oxymorphone
      • Paliperidone
      • Pemoline
      • Pentazocine
      • Pentazocine; Naloxone
      • Perphenazine
      • Perphenazine; Amitriptyline
      • Phendimetrazine
      • Phentermine
      • Phentermine; Topiramate
      • Phenylephrine; Promethazine
      • Pitolisant
      • Prochlorperazine
      • Promethazine
      • Propafenone
      • Propoxyphene
      • Protriptyline
      • Pseudoephedrine
      • Remifentanil
      • Risperidone
      • Sodium Oxybate
      • Sufentanil
      • Tapentadol
      • Theophylline, Aminophylline
      • Thiethylperazine
      • Thiothixene
      • Tramadol
      • Tricyclic antidepressants
      • Trifluoperazine
      • Trimipramine
      • Vortioxetine
      • Ziprasidone

      Level 3 (Moderate)

      • Acetaminophen; Aspirin, ASA; Caffeine
      • Acetaminophen; Butalbital
      • Acetaminophen; Butalbital; Caffeine
      • Acetaminophen; Caffeine
      • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
      • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
      • Acetazolamide
      • Alosetron
      • Amobarbital
      • Anticonvulsants
      • Aspirin, ASA; Butalbital; Caffeine
      • Aspirin, ASA; Caffeine; Orphenadrine
      • Atazanavir; Cobicistat
      • Atropine
      • Atropine; Edrophonium
      • Atropine; Hyoscyamine; Phenobarbital; Scopolamine
      • Azelastine; Fluticasone
      • Barbiturates
      • Beclomethasone
      • Belladonna Alkaloids; Ergotamine; Phenobarbital
      • Benztropine
      • Betamethasone
      • Bethanechol
      • Budesonide
      • Budesonide; Formoterol
      • Budesonide; Glycopyrrolate; Formoterol
      • Butabarbital
      • Caffeine
      • Caffeine; Ergotamine
      • Cannabidiol
      • Carbamazepine
      • Cevimeline
      • Chlordiazepoxide; Clidinium
      • Ciclesonide
      • Cimetidine
      • Citalopram
      • Clopidogrel
      • Cobicistat
      • Corticosteroids
      • Cortisone
      • Dalfampridine
      • Darifenacin
      • Darunavir; Cobicistat
      • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
      • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
      • Deflazacort
      • Dexamethasone
      • Dicyclomine
      • Digoxin
      • Doxercalciferol
      • Dronabinol
      • Duloxetine
      • Dutasteride; Tamsulosin
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Ethotoin
      • Fenfluramine
      • Flavoxate
      • Fludrocortisone
      • Flunisolide
      • Fluoxetine
      • Fluticasone
      • Fluticasone; Salmeterol
      • Fluticasone; Umeclidinium; Vilanterol
      • Fluticasone; Vilanterol
      • Fluvoxamine
      • Formoterol; Mometasone
      • Fosphenytoin
      • Gabapentin
      • Gefitinib
      • Glycopyrrolate
      • Glycopyrrolate; Formoterol
      • Guanfacine
      • Hydantoins
      • Hydrochlorothiazide, HCTZ; Metoprolol
      • Hydrocortisone
      • Hyoscyamine
      • Indacaterol; Glycopyrrolate
      • Isavuconazonium
      • Isoniazid, INH
      • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
      • Isoniazid, INH; Rifampin
      • Ivosidenib
      • Lacosamide
      • Lamotrigine
      • Lasmiditan
      • Lemborexant
      • Levetiracetam
      • Loperamide
      • Loperamide; Simethicone
      • Lopinavir; Ritonavir
      • Lorcaserin
      • Lumacaftor; Ivacaftor
      • Lumacaftor; Ivacaftor
      • Mepenzolate
      • Mephobarbital
      • Methohexital
      • Methscopolamine
      • Methylprednisolone
      • Metoprolol
      • Midazolam
      • Mifepristone
      • Mometasone
      • Nabilone
      • Nebivolol
      • Nebivolol; Valsartan
      • Nicotine
      • Oliceridine
      • Ombitasvir; Paritaprevir; Ritonavir
      • Oxcarbazepine
      • Oxybutynin
      • Paroxetine
      • Pentobarbital
      • Phenobarbital
      • Phenothiazines
      • Phenytoin
      • Prednisolone
      • Prednisone
      • Primidone
      • Propantheline
      • Ranolazine
      • Rifampin
      • Ritonavir
      • Scopolamine
      • Secobarbital
      • Sertraline
      • Solriamfetol
      • Tamoxifen
      • Tamsulosin
      • Thiopental
      • Thiotepa
      • Tiagabine
      • Ticlopidine
      • tobacco
      • Tolterodine
      • Topiramate
      • Triamcinolone
      • Triazolam
      • Trihexyphenidyl
      • Trospium
      • Valproic Acid, Divalproex Sodium
      • Vigabatrin
      • Warfarin
      • Zolpidem
      • Zonisamide

      Level 4 (Minor)

      • Acamprosate
      • Brimonidine; Timolol
      • Carvedilol
      • Dorzolamide; Timolol
      • Hydrochlorothiazide, HCTZ; Propranolol
      • Nelfinavir
      • Nitroglycerin
      • Propranolol
      • Timolol
      Acamprosate: (Minor) The administration of naltrexone with acamprosate results in an increase in acamprosate exposure (AUC) by 25% and in peak concentration (Cmax) by 33%. However, acamprosate dosage adjustments are not required. [49185] Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Acetaminophen; Butalbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Acetaminophen; Butalbital; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Acetaminophen; Butalbital; Caffeine; Codeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] [7089] (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Acetaminophen; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Acetaminophen; Caffeine; Dihydrocodeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6925] [6993] [8203] (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] (Moderate) Concomitant use of dihydrocodeine with bupropion may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of bupropion could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Bupropion is a strong inhibitor of CYP2D6. [30282] [41057] Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Acetaminophen; Codeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] [7089] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Acetaminophen; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Acetaminophen; Oxycodone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as oxycodone may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Acetaminophen; Pentazocine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [56099] (Moderate) Plasma concentrations of opiate agents metabolized by CYP2D6, such as pentazocine, may be increased if bupropion, an inhibitor of the CYP2D6 isoenzyme, is added. Dosage reductions of pentazocine may be needed. Conversely, if bupropion therapy is discontinued, dosages of pentazocine may need to be adjusted upward in some patients. [2173] Acetaminophen; Propoxyphene: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6705] [6993] (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as propoxyphene may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Acetaminophen; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Acetaminophen; Tramadol: (Major) Increased serum concentrations of tramadol and reduced serum concentrations of the O-desmethyltramadol metabolite (M1) would be expected from concurrent use of tramadol and a CYP2D6 inhibitor such as bupropion. As the analgesic activity of tramadol is due to both the parent drug and M1, inhibition of CYP2D6 by bupropion may affect the analgesic effect of tramadol; reduced analgesic effects are possible. Also, administration of tramadol may enhance the seizure risk in patients taking other medications that decrease the seizure threshold such as bupropion. [28001] [28314] Acetazolamide: (Moderate) It should be noted that when anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), that bupropion should not be used by patients with a preexisting seizure disorde; this represents a disease-drug interaction, and not a drug-drug interaction per se. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions. Addiive CNS effects are possible, and the patient may feel dizzy, drowsy or more tired when taking these drugs together. [28058] [40993] [41086] [44094] Acrivastine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Alfentanil: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. The usual doses of alfentanil will be ineffective in patients receiving naltrexone. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. However, respiratory depression from alfentanil is not expected to last longer than the effect of a single naloxone dose. Other non-opioid medications should be used prior to, during, and after surgery as increased doses of opiate agonists are required to override the antagonistic effects of naltrexone and may induce prolonged and more severe adverse effects. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] (Moderate) If concomitant use of alfentanil and bupropion is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [30072] Alosetron: (Moderate) Alosetron, if used with drugs that have anticholinergic effects such as bupropion, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid these drugs in patients taking alosetron. [28382] Alvimopan: (Major) Alvimopan is an opiate antagonist. In general, coadministration with another opiate antagonist should be avoided due to the potential for additive effect of opioid receptor antagonism and increased risk of opioid withdrawal with concomitant use. [34103] [34117] [57937] Amantadine: (Major) Use caution when concurrently administering bupropion and amantadine; if concurrent use is necessary, low initial dosing and slow dosage titration of bupropion should be considered. Both bupropion and amantadine have dopamine agonist effects, and coadministration may result in additive CNS dopaminergic effects. Reported adverse reactions have included neurologic side effects such as restlessness, agitation, gait disturbance, vertigo, and dizziness; some patients have required hospitalization. In reported cases, discontinuation of the drugs resulted in symptom resolution. [41057] Amifampridine: (Major) Carefully consider the need for concomitant treatment with bupropion and amifampridine, as coadministration may increase the risk of seizures. Consider alternatives to bupropion. If use together is medically necessary, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Bupropion is known to have a dose-dependent risk for seizures. [41057] [41086] [44094] [44095] [46944] [57922] [63790] Amitriptyline: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Amitriptyline; Chlordiazepoxide: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Amobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Amoxapine: (Major) Concurrent administration of amoxapine with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus may reduce the clearance of amoxapine leading to a potential for increased Cmax, AUC and half-life. Amoxapine appears to be metabolized via CYP2D6. Low initial dosing and gradual dose increases of both drugs should be employed. If bupropion is added to a regimen of a patient already receiving amoxapine, the need to reduce the amoxapine dosage should be considered. [28558] [4718] [4781] Amphetamine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41086] [60070] Amphetamine; Dextroamphetamine Salts: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41086] [60070] Amphetamine; Dextroamphetamine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41086] [60070] Anticonvulsants: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094] Aripiprazole: (Major) Because aripiprazole is partially metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP2D6 such as bupropion. Closely monitor for evidence of aripiprazole adverse events. Additionally, bupropion is associated with a dose-related risk of seizure; antipsychotics may increase this risk. In adults receiving 300 mg or 400 mg of Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if a strong CYP2D6 inhibitor is used for more than 14 days. Adults receiving 662 mg or 882 mg of Aristada every 4 weeks should have their Aristada dose reduced to the next lower strength if a strong CYP2D6 inhibitor is used for more than 14 days. For patients receiving Aristada 882 mg every 6 weeks or 1,064 mg every 2 months, reduce the dose to 441 mg every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated. Because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Avoid use of combination therapy with a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor for more than 14 days in patients receiving 662 mg, 882 mg, or 1,064 mg of Aristada; no dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated. Avoid concurrent use of Aristada Initio and strong CYP2D6 inhibitors because the dose of Aristada Initio cannot be modified. [41057] [42845] [53394] [60196] [62642] [63328] Armodafinil: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [4781] Asenapine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [36343] [41057] Aspirin, ASA; Butalbital; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] [7089] (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Aspirin, ASA; Caffeine; Dihydrocodeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6925] [6993] [8203] (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] (Moderate) Concomitant use of dihydrocodeine with bupropion may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of bupropion could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Bupropion is a strong inhibitor of CYP2D6. [30282] [41057] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Aspirin, ASA; Carisoprodol; Codeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] [7089] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Aspirin, ASA; Oxycodone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as oxycodone may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Atazanavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. [41057] [51664] [58000] Atomoxetine: (Major) Dosage reduction of atomoxetine is recommended in patients receiving bupropion due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving bupropion, atomoxetine should be initiated at 0.5 mg/kg/day and only increased to the usual target dose of 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well-tolerated. In children and adolescents over 70 kg and adults receiving bupropion, atomoxetine should be initiated at 40 mg/day and only increased to the usual target dose of 80 mg/day if symptoms fail to improve after 4 weeks and the initial dose is well-tolerated. Bupropion is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure. [28405] Atropine: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28058] [28714] [30291] Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Severe) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. [41086] (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30425] (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28058] [28714] [30291] Atropine; Difenoxin: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] [7021] (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28058] [28714] [30291] Atropine; Diphenoxylate: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] [7021] (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28058] [28714] [30291] Atropine; Edrophonium: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28058] [28714] [30291] Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30425] (Moderate) Additive anticholinergic effects may be seen when scopolamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30354] (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28058] [28714] [30291] Azelastine; Fluticasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Barbiturates: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Beclomethasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Severe) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. [41086] (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30425] Benzphetamine: (Major) The risk of seizures from the use of bupropion may be increased with concomitant use of CNS stimulants and anorectics that may induce seizures, including benzphetamine. Concurrent use is not recommended. Extreme caution and close clinical monitoring is recommended if these agents must be used together. [4781] [5043] Benztropine: (Moderate) Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as bupropion. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28001] [30312] Betamethasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Bethanechol: (Moderate) Bupropion exhibits moderate anticholinergic properties. Avoid co-use when possible since the effects of bethanechol, a cholinergic agonist, may be diminished. If co-use is necessary, monitor for the intended clinical response. [24817] [29597] [29831] Bremelanotide: (Major) Avoid using bremelanotide with an orally-administered naltrexone-containing product that is intended to treat alcohol and opioid addiction due to the severe consequence of naltrexone treatment failure. In pharmacokinetic studies, bremelanotide significantly affected the oral absorption of naltrexone. [64337] Brexpiprazole: (Major) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-half of the usual dose in patients receiving a strong CYP2D6 inhibitor and one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Bupropion is a strong inhibitor of CYP2D6. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. It should be noted that no dosage adjustment is needed in patients taking a strong CYP2D6 inhibitor who are receiving brexpiprazole as adjunct treatment for major depressive disorder because CYP2D6 considerations are already factored into general dosing recommendations. [41057] [59949] Brimonidine; Timolol: (Minor) Monitor for an increased incidence of timolol-related adverse effects if bupropion and timolol are used concomitantly. Coadministration of bupropion and timolol may result in increased plasma concentrations of timolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Timolol is a CYP2D6 substrate. [28540] [41057] Brompheniramine; Guaifenesin; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Brompheniramine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Budesonide: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Budesonide; Formoterol: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Budesonide; Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [30355] (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Buprenorphine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [56099] (Moderate) If concomitant use of buprenorphine and bupropion is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [60270] Buprenorphine; Naloxone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [56099] (Moderate) If concomitant use of buprenorphine and bupropion is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [60270] Butabarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Butorphanol: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [56099] Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Caffeine; Ergotamine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as sodium oxybate. The risk of seizures with bupropion is dose related and is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment If used together, use low initial doses of bupropion and increase the dose gradually. [28528] [41057] Cannabidiol: (Moderate) Consider a dose adjustment of bupropion when coadministered with cannabidiol. Coadministration may alter plasma concentrations of bupropion resulting in an increased risk of adverse reactions and/or decreased efficacy. Bupropion is a substrate of CYP2B6; cannabidiol may inhibit and/or induce CYP2B6 at clinically relevant concentrations. [41507] [63309] Carbamazepine: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Carbamazepine induces hepatic enzymes and may lower bupropion exposure. Bupropion is a sensitive substrate of CYP2B6, and carbamazepine is a potent inducer for this enzyme. Monitor for signs of reduced bupropion efficacy during use together. Also monitor for any changes in seizure status if carbamazepine is used to treat seizures. [27843] [28058] [40993] [41086] [44094] Carbetapentane; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Carbidopa; Levodopa: (Major) Use bupropion cautiously in patients taking levodopa or combination drugs containing levodopa (e.g., carbidopa; levodopa and carbidopa; levodopa; entacapone). Both drugs are dopamine agonists; cumulative effects may result in central nervous system (CNS) toxicity. Adverse reactions reported with coadministration have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. If levodopa is used concurrently, low initial dosing and slow dosage titration of bupropion may be warranted. [41057] Carbidopa; Levodopa; Entacapone: (Major) Use bupropion cautiously in patients taking levodopa or combination drugs containing levodopa (e.g., carbidopa; levodopa and carbidopa; levodopa; entacapone). Both drugs are dopamine agonists; cumulative effects may result in central nervous system (CNS) toxicity. Adverse reactions reported with coadministration have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. If levodopa is used concurrently, low initial dosing and slow dosage titration of bupropion may be warranted. [41057] Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Carbinoxamine; Hydrocodone; Phenylephrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Carbinoxamine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Cariprazine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [41057] [60164] Carvedilol: (Minor) Monitor for an increased incidence of carvedilol-related adverse effects if bupropion and carvedilol are used concomitantly. Coadministration of bupropion and carvedilol may result in increased plasma concentrations of carvedilol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Carvedilol is a CYP2D6 substrate. [28537] [41057] Cenobamate: (Major) Increase the dosage of bupropion as needed when coadministered with cenobamate due to the potential for reduced efficacy of bupropion. Multiple doses of cenobamate decreased bupropion exposure by 39%. Bupropion is a sensitive substrate of CYP2B6; cenobamate is a weak CYP2B6 inducer. [40993] [64768] Cetirizine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Cevimeline: (Moderate) Cevimeline is partially metabolized by CYP2D6. Inhibitors of this isoenzyme, like bupropion, would be expected to lead to an increase in cevimeline plasma concentrations. [28001] Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Chlordiazepoxide; Clidinium: (Moderate) Bupropion exhibits moderate anticholinergic effects. Clinicians should consider this when using antimuscarinics and other medications with anticholinergic activity in combination with bupropion. [28058] Chlorpheniramine; Codeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] [7089] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6925] [6993] [8203] (Moderate) Concomitant use of dihydrocodeine with bupropion may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of bupropion could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Bupropion is a strong inhibitor of CYP2D6. [30282] [41057] Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6925] [6993] [8203] (Moderate) Concomitant use of dihydrocodeine with bupropion may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of bupropion could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Bupropion is a strong inhibitor of CYP2D6. [30282] [41057] Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Chlorpheniramine; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Chlorpheniramine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Chlorpromazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of chlorpromazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of chlorpromazine may result in QT prolongation, somnolence, anticholinergic effects, or orthostasis. [28997] [41057] Ciclesonide: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Cimetidine: (Moderate) Cimetidine has resulted in increased plasma concentrations of the active metabolites, threohydrobupropion and erythrobupropion, but the clinical significance is not known. [4718] Citalopram: (Moderate) A pharmacokinetic interaction has been observed between bupropion and citalopram. In one study, bupropion increased the Cmax and AUC of citalopram by 30% and 40%, respectively. Citalopram did not affect the kinetics of bupropion or its metabolites. The mechanism of this interaction has not been clearly established since citalopram is primarily metabolized by the isoenzymes CYP3A4 and CYP2C19 and bupropion and its metabolite hydroxybupropion are metabolized by CYP2B6 and are inhibitors of CYP2D6. [28058] [28269] Clomipramine: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Clopidogrel: (Moderate) Dosage adjustment of bupropion may be necessary during coadministration with clopidogrel. Concomitant use may increase bupropion exposure but decrease hydroxybupropion exposure. Bupropion is primarily metabolized to hydroxybupropion via CYP2B6; clopidogrel is a weak CYP2B6 inhibitor. [34691] [41057] [56579] Clozapine: (Major) Monitor for evidence of clozapine-related adverse reactions and consider a clozapine dose reduction if necessary when coadministered with bupropion. If bupropion is discontinued after dose adjustments are made, monitor for lack of clozapine affect and consider increasing the clozapine dose if necessary. Concurrent use may result in increased clozapine exposure due to inhibition of CYP2D6 metabolism by bupropion. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Elevated plasma concentrations of clozapine may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. Furthermore, bupropion is associated with a dose-related risk of seizures; this risk may be increased by antipsychotics. [28262] [41057] Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. [41057] [51664] [58000] Cocaine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as cocaine. This is of particular concern in those with excessive cocaine use (i.e., cocaine addition). Patients should be closely monitored if this combination is necessary. [4781] Codeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] [7089] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Codeine; Guaifenesin: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] [7089] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Codeine; Phenylephrine; Promethazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of promethazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of promethazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43930] (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] [7089] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Codeine; Promethazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of promethazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of promethazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43930] (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] [7089] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Corticosteroids: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Cortisone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Cyclobenzaprine: (Major) Concurrent use of cyclobenzaprine with bupropion increases the possibility of developing serotonin syndrome. If these drugs must be used together, closely monitor the patient for signs and symptoms of serotonin syndrome. If such a reaction develops, immediately discontinue both drugs. Additionally, cyclobenzaprine possesses antimuscarinic properties, which can cause dry mouth, urinary difficulties and slowing of gastrointestinal motility. If used with other drugs with antimuscarinic properties, such as bupropion, anticholinergic side effects can be additive. Particular attention should be paid to GI problems because of the possible development of paralytic ileus. [28058] [28425] Dabrafenib: (Major) The concomitant use of dabrafenib and bupropion may lead to decreased bupropion concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of bupropion efficacy. In vitro, dabrafenib is an inducer of CYP2B6 via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Bupropion is a sensitive CYP2B6 substrate. [41057] [54802] Dalfampridine: (Moderate) Due to additive risks for seizure, extreme caution when coadministering bupropion with other drugs that lower seizure threshold (e.g., dalfampridine). Use low initial doses and increase the dose gradually. Monitor for seizure activity. Consider benefits against the risk of seizures. Consider alternatives to bupropion. Additionally, bupropion inhibits OCT2 in vitro, but the clinical relevance is not certain. Concurrent treatment with OCT2 inhibitors, such as bupropion, may cause increased exposure to dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking OCT2 inhibitors concurrently with dalfampridine should be considered against the risk of seizures in these patients. [41086] [41087] [43980] [44095] [57922] Darifenacin: (Moderate) Bupropion, an inhibitor of CYP2D6 may inhibit the metabolism of darifenacin. In addition, bupropion is associated with moderate anticholinergic effects which could be additive when coadministered with darifenacin. Patients should be monitored for increased anticholinergic effects or other adverse effects when these two drugs are coadministered. Dosage adjustments may be necessary. [28001] [28058] [30711] Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. [41057] [51664] [58000] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. [41057] [51664] [58000] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of bupropion with ritonavir results in decreased concentrations of bupropion and its active metabolite. According to the manufacturers of bupropion, increased doses of bupropion may be necessary during concurrent therapy; however, the maximum recommended dose of bupropion should not be exceeded. Closely monitor bupropion efficacy if these drugs are given together. Ritonavir induces CYP2B6, which is responsible for bupropion's metabolism. In one study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. In addition, exposure to the active metabolite of bupropion (hydroxybupropion) was decreased by 23%. When given with ritonavir 600 mg twice daily, the AUC and Cmax of bupropion decreased by 66% and 63% respectively and exposure to hydroxybupropion decreased by 78%. [28058] [28315] [34743] [34744] [34745] [34746] [44095] Deflazacort: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Desipramine: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Desloratadine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Deutetrabenazine: (Major) Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if must use concurrently with a strong CYP2D6 inhibitor. Bupropion is a strong CYP2D6 inhibitor, and the metabolites of deutetrabenazine, alpha- and beta-HTBZ, are CYP2D6 substrates. The systemic exposure of alpha- and beta-HTBZ may be increased resulting in an increase in deutetrabenazine-related adverse reactions, like QT prolongation and drowsiness. [61845] Dexamethasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Dexmethylphenidate: (Major) Drugs that may lower the seizure threshold, such as dexmethylphenidate, should be used cautiously in patients taking bupropion, an antidepressant with a dose-related risk of seizures. Patients should be closely monitored if this combination is necessary. [28519] [41057] Dextroamphetamine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41086] [60070] Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Dextromethorphan; Promethazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of promethazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of promethazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43930] Dicyclomine: (Moderate) Additive anticholinergic effects may be seen when dicyclomine is used concomitantly with other drugs that possess anticholinergic properties, such as bupropion. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [30090] Diethylpropion: (Major) Drugs which may lower the seizure threshold, such as diethylpropion, should be used with great caution or avoided in patients taking bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if this combination must be used concurrently; the patient should be closely monitored. [41057] Digoxin: (Moderate) Plasma digoxin concentrations and the patient's clinical response to digoxin therapy should be monitored during concurrent use with bupropion, due to the potential for decreased systemic exposure to digoxin. When a single oral dose of 0.5 mg of digoxin was administered 24 hours after a single 150 mg oral dose of extended-release bupropion in healthy volunteers, the digoxin exposure was decreased. [40993] [41086] Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6925] [6993] [8203] (Moderate) Concomitant use of dihydrocodeine with bupropion may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of bupropion could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Bupropion is a strong inhibitor of CYP2D6. [30282] [41057] Diphenhydramine; Hydrocodone; Phenylephrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Disulfiram: (Major) The safety and efficacy of concomitant use of naltrexone and disulfiram is unknown. There is the possibility of additive hepatotoxicity and concurrent use of these agents is not recommended. If concomitant use of naltrexone and disulfiram is required, liver function tests should be performed prior to beginning combination therapy, then they should be repeated every 2 weeks for 1 to 2 months. Continue monitoring LFTs monthly after the third month of combined use. [5887] Dorzolamide; Timolol: (Minor) Monitor for an increased incidence of timolol-related adverse effects if bupropion and timolol are used concomitantly. Coadministration of bupropion and timolol may result in increased plasma concentrations of timolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Timolol is a CYP2D6 substrate. [28540] [41057] Doxepin: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Doxercalciferol: (Moderate) CYP450 enzyme inhibitors, like bupropion, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if cytochrome P450 inhibitors are coadministered with doxercalciferol. [30802] [51248] Doxorubicin: (Major) In vitro, bupropion is a mild CYP2D6 inhibitor and doxorubicin is a major CYP2D6 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of bupropion and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity. [41057] [56361] Dronabinol: (Moderate) Concomitant administration of naltrexone and oral THC like dronabinol enhances the positive subjective effects of oral THC. Data from separate investigations demonstrate that pretreatment with an opioid receptor blocker such as naltrexone significantly increases many of the euphoric effects of oral THC in heavy marijuana smokers. [32226] [32231] Duloxetine: (Moderate) Monitor for increased duloxetine-related adverse effects if coadministered with bupropion. Concurrent use may result in increased duloxetine exposure resulting in excessive serotonin activity. Bupropion is a strong CYP2D6 inhibitor; duloxetine is a CYP2D6 substrate. Coadministration with another strong CYP2D6 inhibitor increased the duloxetine AUC by about 60%. [28058] [29934] Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as bupropion. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects. [28001] [28058] [29677] Efavirenz: (Major) Concurrent use of efavirenz 600 mg/day and bupropion in healthy volunteers resulted in a reduction of the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged and the Cmax of hydroxybupropion was increased by 50%. Healthcare providers are advised to increase the dose of bupropion based on clinical response during concurrent use with efavirenz; however, the maximum recommended dose of bupropion should not be exceeded. [28442] [32514] [40993] Efavirenz; Emtricitabine; Tenofovir: (Major) Concurrent use of efavirenz 600 mg/day and bupropion in healthy volunteers resulted in a reduction of the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged and the Cmax of hydroxybupropion was increased by 50%. Healthcare providers are advised to increase the dose of bupropion based on clinical response during concurrent use with efavirenz; however, the maximum recommended dose of bupropion should not be exceeded. [28442] [32514] [40993] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Concurrent use of efavirenz 600 mg/day and bupropion in healthy volunteers resulted in a reduction of the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged and the Cmax of hydroxybupropion was increased by 50%. Healthcare providers are advised to increase the dose of bupropion based on clinical response during concurrent use with efavirenz; however, the maximum recommended dose of bupropion should not be exceeded. [28442] [32514] [40993] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. [41057] [51664] [58000] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. [41057] [51664] [58000] Encainide: (Major) Encainide is significantly metabolized by CYP2D6 isoenzymes. Caution is recommended when administering encainide with CYP2D6 inhibitors, such as bupropion, since encainide exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions. [28001] [28058] Ethanol: (Major) Bupropion is associated with a dose-related risk of seizures. Both ethanol abuse and abrupt discontinuation of ethanol have been associated with seizures and fatalities, and may increase the risk of seizures and/or neuropsychiatric events with bupropion treatment. The use of ethanol or the abrupt discontinuation of ethanol should be avoided in patients taking bupropion. During post-marketing use of bupropion, some patients who were drinking alcohol reported reduced alcohol tolerance. [28058] [28449] Ethotoin: (Moderate) When anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), bupropion should not be used since bupropion lowers the seizure threshold. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions (e.g., neuropathic pain, mood disorders). Bupropion may interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as phenytoin (as well as other hydantoins like fosphenytoin or ethotoin). Monitor for reduced bupropion efficacy. [28058] [28535] [28823] [40993] [41086] [44094] Felbamate: (Major) Bupropion should not be used by patients taking anticonvulsants for seizures because it may decrease the seizure threshold. Bupropion may also interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [4781] Fenfluramine: (Moderate) Use fenfluramine and bupropion with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [63529] [65634] Fentanyl: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6365] [6993] (Moderate) If concomitant use of fentanyl and bupropion is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [40944] Fexofenadine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Flavoxate: (Moderate) Bupropion exhibits moderate anticholinergic effects. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with bupropion. [4781] Flecainide: (Major) Flecainide is significantly metabolized by CYP2D6 isoenzymes. Caution is recommended when administering flecainide with CYP2D6 inhibitors, such as bupropion; flecainide exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions. [4718] [4781] Fludrocortisone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Flunisolide: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Fluoxetine: (Moderate) Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by CYP2D6 should be approached with caution. Many selective serotonin reuptake inhibitors (SSRIs) are CYP2D6 substrates including fluoxetine. Although clinical evidence of interactions is lacking, plasma concentrations of SSRIs metabolized by CYP2D6 may be increased if bupropion is added. [28001] [28058] Fluoxetine; Olanzapine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [28785] [41057] (Moderate) Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by CYP2D6 should be approached with caution. Many selective serotonin reuptake inhibitors (SSRIs) are CYP2D6 substrates including fluoxetine. Although clinical evidence of interactions is lacking, plasma concentrations of SSRIs metabolized by CYP2D6 may be increased if bupropion is added. [28001] [28058] Fluphenazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of fluphenazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of fluphenazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43067] Fluticasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Fluticasone; Salmeterol: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Fluticasone; Umeclidinium; Vilanterol: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Fluticasone; Vilanterol: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Fluvoxamine: (Moderate) Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by CYP2D6 should be approached with caution. Many selective serotonin reuptake inhibitors (SSRIs) are CYP2D6 substrates including fluvoxamine. Although clinical evidence of interactions is lacking, plasma concentrations of SSRIs metabolized by CYP2D6 may be increased if bupropion is added. In addition, in vitro studies suggest that fluvoxamine inhibits the hydroxylation of bupropion. [28058] Formoterol; Mometasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Fosphenytoin: (Moderate) When anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), bupropion should not be used since bupropion lowers the seizure threshold. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions (e.g., neuropathic pain, mood disorders). Bupropion may interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as phenytoin (as well as other hydantoins like fosphenytoin or ethotoin). Monitor for reduced bupropion efficacy. [28058] [28535] [28823] [40993] [41086] [44094] Gabapentin: (Moderate) A reduction in seizure threshold has been reported following concomitant administration of pemoline with anticonvulsant agents. [28058] [40993] [41086] [44094] Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with bupropion is necessary; the risk is increased in CYP2D6 poor metabolizers. Based on in vitro data, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and bupropion is a strong CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism. [41057] [45935] Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [30355] Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [30355] Guaifenesin; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Guaifenesin; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Guanfacine: (Moderate) There is one case report that describes a grand mal seizure that occurred in a child of 10 years of age receiving guanfacine and bupropion concurrently. It is not possible, based on this limited report, to determine if guanfacine was a contributor to the event. Causality has not been established. [28455] Haloperidol: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by the CYP2D6 isoenzyme, such as haloperidol, should be approached with caution. Dosage reductions of haloperidol may be needed. Conversely, if bupropion therapy is discontinued, the antipsychotic dosage may need to be increased in some patients. [41057] Homatropine; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Additive anticholinergic effects may be seen when homatropine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [26665] [28058] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydantoins: (Moderate) When anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), bupropion should not be used since bupropion lowers the seizure threshold. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions (e.g., neuropathic pain, mood disorders). Bupropion may interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as phenytoin (as well as other hydantoins like fosphenytoin or ethotoin). Monitor for reduced bupropion efficacy. [28058] [28535] [28823] [40993] [41086] [44094] Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration of bupropion. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure and decrease its cardioselectivity. Metoprolol is a CYP2D6 substrate; bupropion is a strong CYP2D6 inhibitor. In the presence of another strong CYP2D6 inhibitor, the concentration of S-metoprolol was tripled and the metoprolol elimination half-life doubled. [28539] [32916] [41057] Hydrochlorothiazide, HCTZ; Propranolol: (Minor) Monitor for an increased incidence of propranolol-related adverse effects if bupropion and propranolol are used concomitantly. Coadministration of bupropion and propranolol may result in increased plasma concentrations of propranolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Propranolol is a CYP2D6 substrate. [41057] [53617] Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydrocodone; Ibuprofen: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydrocodone; Phenylephrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydrocodone; Potassium Guaiacolsulfonate: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydrocodone; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone. [56303] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydrocortisone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Hydromorphone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Opiate antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to hydromorphone. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [39635] [6993] [7129] (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30425] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Severe) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. [41086] (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30425] Ibuprofen; Oxycodone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as oxycodone may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Ibuprofen; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Iloperidone: (Major) Reduce the iloperidone dose by one-half if coadministered with bupropion. If bupropion is discontinued, increase the iloperidone dose to the previous level. Increased iloperidone exposure may occur with concurrent use. Additionally, bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. Iloperidone is a CYP2D6 substrate. Bupropion is a strong inhibitor of CYP2D6. Coadministration of other strong CYP2D6 inhibitors increased mean steady-state peak concentrations of iloperidone and its metabolite P88, by up to 3-fold, and decreased mean steady-state peak concentrations of its metabolite P95 by one-half. [36146] [41057] Imipramine: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Indacaterol; Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [30355] Iobenguane I 131: (Major) Discontinue bupropion for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart bupropion until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as bupropion, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy. [63402] Isavuconazonium: (Moderate) Caution and close monitoring are advised when administering isavuconazonium concurrently with buproprion, as decreased buproprion serum concentrations may result. If decreased bupropion efficacy is noted, it may be necessary to increase the dose (not to exceed the maximum recommended dose). Isavuconazole, the active moiety of isavuconazonium, is an inducer of hepatic isoenzyme CYP2B6; bupropion is metabolized by this enzyme. [41086] [59042] Isocarboxazid: (Severe) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs. [28058] [40993] [41086] [44094] [57922] Isoniazid, INH: (Moderate) In theory, concurrent use of bupropion and isoniazid, INH may result in a hypertensive reaction. Bupropion increases monoamine neurotransmitter levels (dopamine and norepinephrine) through reuptake inhibition and isoniazid is a weak inhibitor of monoamine oxidase (MAO), an enzyme system which contributes to the degradation of monoamine neurotransmitters. The risk of hypertension is increased if bupropion is administered with monoamine oxidase inhibitors (MAOIs) or other drugs that increase dopaminergic or noradrenergic activity. Although the manufacturer of bupropion makes no recommendations regarding isoniazid, bupropion is contraindicated for use with MAOIs intended to treat psychiatric disorders (e.g., phenelzine) as well as other drugs with MAOI activity (e.g., linezolid, methylene blue). [24822] [41086] Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours. [28001] [32802] (Moderate) In theory, concurrent use of bupropion and isoniazid, INH may result in a hypertensive reaction. Bupropion increases monoamine neurotransmitter levels (dopamine and norepinephrine) through reuptake inhibition and isoniazid is a weak inhibitor of monoamine oxidase (MAO), an enzyme system which contributes to the degradation of monoamine neurotransmitters. The risk of hypertension is increased if bupropion is administered with monoamine oxidase inhibitors (MAOIs) or other drugs that increase dopaminergic or noradrenergic activity. Although the manufacturer of bupropion makes no recommendations regarding isoniazid, bupropion is contraindicated for use with MAOIs intended to treat psychiatric disorders (e.g., phenelzine) as well as other drugs with MAOI activity (e.g., linezolid, methylene blue). [24822] [41086] Isoniazid, INH; Rifampin: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours. [28001] [32802] (Moderate) In theory, concurrent use of bupropion and isoniazid, INH may result in a hypertensive reaction. Bupropion increases monoamine neurotransmitter levels (dopamine and norepinephrine) through reuptake inhibition and isoniazid is a weak inhibitor of monoamine oxidase (MAO), an enzyme system which contributes to the degradation of monoamine neurotransmitters. The risk of hypertension is increased if bupropion is administered with monoamine oxidase inhibitors (MAOIs) or other drugs that increase dopaminergic or noradrenergic activity. Although the manufacturer of bupropion makes no recommendations regarding isoniazid, bupropion is contraindicated for use with MAOIs intended to treat psychiatric disorders (e.g., phenelzine) as well as other drugs with MAOI activity (e.g., linezolid, methylene blue). [24822] [41086] Ivosidenib: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of ivosidenib. A bupropion dose increase may be necessary; do not exceed the maximum recommended dose. Bupropion is a sensitive substrate of CYP2B6; ivosidenib may induce CYP2B6 leading to decreased bupropion concentrations. [41057] [63368] Lacosamide: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094] Lamotrigine: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094] Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and bupropion. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. [63529] [64685] Lemborexant: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of lemborexant as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose for the specific product prescribed. Bupropion is a sensitive substrate of CYP2B6; lemborexant is a weak CYP2B6 inducer. [40993] [41057] [41086] [44094] [44095] [56579] [64870] Levetiracetam: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094] Levodopa: (Major) Use bupropion cautiously in patients taking levodopa or combination drugs containing levodopa (e.g., carbidopa; levodopa and carbidopa; levodopa; entacapone). Both drugs are dopamine agonists; cumulative effects may result in central nervous system (CNS) toxicity. Adverse reactions reported with coadministration have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. If levodopa is used concurrently, low initial dosing and slow dosage titration of bupropion may be warranted. [41057] Levomethadyl: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] Levorphanol: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] Linezolid: (Severe) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving linezolid, an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with linezolid, bupropion should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of linezolid. [41086] Lisdexamfetamine: (Major) The risk of seizures from the use of bupropion may be increased with concomitant use of CNS stimulants that may induce seizures, including the lisdexamfetamine. Concurrent use is not recommended. Extreme caution and close clinical monitoring is recommended if these agents must be used together. [41057] Lofexidine: (Major) Separate administration of lofexidine and oral naltrexone by 2 hours as simultaneous administration may reduce the efficacy of naltrexone. Coadministration of lofexidine and oral naltrexone resulted in statistically significant differences in the steady state pharmacokinetics of naltrexone. This interaction is not expected if naltrexone is administered by non-oral routes. [63161] (Moderate) Monitor for orthostatic hypotension and bradycardia during concurrent use of lofexidine and bupropion. Coadministration may increase lofexidine exposure. Lofexidine is a CYP2D6 substrate; bupropion is a strong CYP2D6 inhibitor. Coadministration with a strong CYP2D6 inhibitor increased the lofexidine AUC by 28%. [41057] [63161] Loperamide: (Moderate) The plasma concentration of loperamide, a CYP2D6 substrate, may be increased when administered concurrently with bupropion, a weak in vitro CYP2D6 inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest). [30106] [41057] [60864] Loperamide; Simethicone: (Moderate) The plasma concentration of loperamide, a CYP2D6 substrate, may be increased when administered concurrently with bupropion, a weak in vitro CYP2D6 inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest). [30106] [41057] [60864] Lopinavir; Ritonavir: (Moderate) Concurrent administration of bupropion with ritonavir results in decreased concentrations of bupropion and its active metabolite. According to the manufacturers of bupropion, increased doses of bupropion may be necessary during concurrent therapy; however, the maximum recommended dose of bupropion should not be exceeded. Closely monitor bupropion efficacy if these drugs are given together. Ritonavir induces CYP2B6, which is responsible for bupropion's metabolism. In one study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. In addition, exposure to the active metabolite of bupropion (hydroxybupropion) was decreased by 23%. When given with ritonavir 600 mg twice daily, the AUC and Cmax of bupropion decreased by 66% and 63% respectively and exposure to hydroxybupropion decreased by 78%. [28058] [28315] [34743] [34744] [34745] [34746] [44095] Loratadine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Lorcaserin: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, bupropion. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms. [51065] Loxapine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [41057] Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of bupropion by decreasing its systemic exposure. If used together, monitor patients closely for loss of bupropion efficacy; a bupropion dosage adjustment may be required to obtain the desired therapeutic effect. Do not exceed the maximum recommended dose. Bupropion is a substrate of CYP2B6; in vitro data suggest that lumacaftor may induce this enzyme. [41057] [59891] Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of bupropion by decreasing its systemic exposure. If used together, monitor patients closely for loss of bupropion efficacy; a bupropion dosage adjustment may be required to obtain the desired therapeutic effect. Do not exceed the maximum recommended dose. Bupropion is a substrate of CYP2B6; in vitro data suggest that lumacaftor may induce this enzyme. [41057] [59891] Lurasidone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [41057] [42227] Maprotiline: (Major) Concurrent administration of maprotiline with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus may reduce the clearance of maprotiline leading to a potential for increased Cmax, AUC and half-life. Maprotiline appears to be metabolized via CYP2D6. Low initial dosing and gradual dose increases of both drugs should be employed. If bupropion is added to a regimen of a patient already receiving maprotiline, the need to reduce the maprotiline dosage should be considered. [4718] [4781] [5542] Mepenzolate: (Moderate) Additive anticholinergic effects may be seen when mepezolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [30076] [42281] Meperidine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Meperidine; Promethazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of promethazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of promethazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43930] (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Mephobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Methadone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as methadone may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28001] [28058] Methamphetamine: (Major) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as methamphetamine. If used together, use low initial doses of bupropion and increase the dose gradually. [33363] [41057] Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Severe) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. [41086] (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30425] Methohexital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Methscopolamine: (Moderate) Additive anticholinergic effects may be seen when methscopolamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [30076] [30424] Methylene Blue: (Severe) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. [41086] Methylnaltrexone: (Major) Avoid coadministration of methylnaltrexone and other opiate antagonists. There is a potential for additive effect of opioid receptor antagonism and increased risk of opioid withdrawal with concomitant use. [34103] Methylphenidate: (Major) Drugs which may lower the seizure threshold, such as methylphenidate, should be used with great caution or avoided in patients taking bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if this combination must be used concurrently; the patient should be closely monitored. [41057] Methylprednisolone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Metoclopramide: (Major) When metoclopramide is used with a potent CYP2D6 inhibitor for the treatment of gastroesophageal reflux (GERD), dosage reductions of oral metoclopramide are required, with maximum oral dosage not to exceed 30 mg/day (e.g., 5 mg 4 times daily or 10 mg 3 times daily). There is a known increase in metoclopramide exposure and an increased risk for extrapyramidal adverse reactions. Metoclopramide is a substrate of CYP2D6 and bupropion is a strong CYP2D6 inhibitor. The manufacturer recommends avoidance of bupropion when oral metoclopramide is used in patients with diabetic gastroparesis. Healthy patients given 20 mg of metoclopramide and a potent CYP2D6 inhibitor for 8 days had a 40% and 90% increase in metoclopramide Cmax and AUC, respectively, compared to patients who received metoclopramide alone. [57877] Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration of bupropion. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure and decrease its cardioselectivity. Metoprolol is a CYP2D6 substrate; bupropion is a strong CYP2D6 inhibitor. In the presence of another strong CYP2D6 inhibitor, the concentration of S-metoprolol was tripled and the metoprolol elimination half-life doubled. [28539] [32916] [41057] Mexiletine: (Major) Coadministration of bupropion and mexiletine can increase the exposure of mexiletine. If used together, it may be necessary to decrease the dose of mexiletine and slowly titrate to effect. Mexiletine is primarily metabolized via CYP2D6 and bupropion and its metabolites are inhibitors of CYP2D6. [28001] [28280] [41057] Midazolam: (Moderate) Bupropion is contraindicated in patients undergoing abrupt withdrawal of benzodiazepines since the risk of seizures associated with bupropion may be increased. Excessive use of benzodiazepines is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. [28058] Mifepristone: (Moderate) Use mifepristone with caution with bupropion. Mifepristone, when used chronically for hormonal conditions such as Cushing's syndrome, is an inhibitor of CYP2B6 and may cause significant increases in exposure of drugs that are metabolized by CYP2B6, such as bupropion. The risk for bupropion-induced adverse reactions, including nausea, dry mouth, restlessness or difficulty with sleep, seizures, hypertension, or neuropsychiatric effects may be increased. Based on clinical response, dosage adjustment of bupropion may be necessary when coadministered with CYP2B6 inhibitors like mifepristone. Due to the slow elimination of mifepristone from the body, any drug interactions that occur may be prolonged. [28003] [48697] Modafinil: (Major) Bupropion is associated with a dose-related risk of seizures. It is unclear whether modafinil lowers the seizure threshold. Seizures have occurred during post-marketing use of modafinil, although the frequency is unknown. [28058] [40907] Molindone: (Major) Drugs which may lower the seizure threshold, such as molindone, should be used with great caution or avoided in patients taking bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if this combination must be used concurrently; the patient should be closely monitored. [28820] Mometasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Monoamine oxidase inhibitors: (Severe) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs. [28058] [40993] [41086] [44094] [57922] Morphine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7 to 10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [56099] (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Morphine; Naltrexone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7 to 10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [56099] (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Nabilone: (Moderate) Concomitant administration of naltrexone and nabilone enhances the 'positive' subjective effects of nabilone. Data from separate investigations demonstrate that pretreatment with an opioid receptor blocker such as naltrexone significantly increases many of the euphoric effects of oral THC in heavy marijuana smokers. [9044] Nalbuphine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [56099] Naldemedine: (Major) Avoid coadministration with other opiate antagonists, like naldemedine. There is a potential for additive effect of opioid receptor antagonism and increased risk of opioid withdrawal with concomitant use. [61831] Naloxegol: (Major) Avoid coadministration of naloxegol and other opiate antagonists. There is a potential for additive effect of opioid receptor antagonism and increased risk of opioid withdrawal with concomitant use. [57937] Naproxen; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with bupropion. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as bupropion, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. [41057] [60860] [60986] [60987] Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with bupropion. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as bupropion, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. [41057] [60860] [60986] [60987] Nelfinavir: (Minor) In vitro studies suggest that nelfinavir inhibits the hydroxylation of bupropion. The clinical significance of this finding is unknown. [40993] Nicotine: (Moderate) Combination of nicotine and bupropion may induce clinically significant blood pressure elevations in some patients. Close monitoring of blood pressure is recommended if this combination is prescribed. [28058] Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants. [45206] Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure. [28963] [30355] [57419] Nortriptyline: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Olanzapine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [28785] [41057] Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and bupropion is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and bupropion may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If bupropion is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [41057] [65809] Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of bupropion with ritonavir results in decreased concentrations of bupropion and its active metabolite. According to the manufacturers of bupropion, increased doses of bupropion may be necessary during concurrent therapy; however, the maximum recommended dose of bupropion should not be exceeded. Closely monitor bupropion efficacy if these drugs are given together. Ritonavir induces CYP2B6, which is responsible for bupropion's metabolism. In one study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. In addition, exposure to the active metabolite of bupropion (hydroxybupropion) was decreased by 23%. When given with ritonavir 600 mg twice daily, the AUC and Cmax of bupropion decreased by 66% and 63% respectively and exposure to hydroxybupropion decreased by 78%. [28058] [28315] [34743] [34744] [34745] [34746] [44095] Opiate Agonists-Antagonists: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [56099] Oxcarbazepine: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. [28058] [40993] [41086] [44094] Oxybutynin: (Moderate) Additive anticholinergic effects may be seen when oxybutynin is used concomitantly with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that anticholinergic effects might be seen not only on bladder smooth muscle, but also on GI function, the eye, and temperature regulation. Additive drowsiness may also occur. [28001] [29597] [29796] Oxycodone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as oxycodone may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Oxymorphone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Naltrexone should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to oxymorphone overdose. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] [9282] (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Ozanimod: (Severe) Coadministration of ozanimod with bupropion is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of bupropion. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Bupropion may increase blood pressure by increasing norepinephrine concentrations. Although bupropion does not inhibit the reuptake of serotonin, it has been associated with cases of serotonin syndrome. Excess serotonin may also contribute to the development of hypertensive crisis. [40993] [63529] [65169] Paliperidone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as paliperidone. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [32936] [41057] Paroxetine: (Moderate) Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by CYP2D6 should be approached with caution. Many selective serotonin reuptake inhibitors (SSRIs) are CYP2D6 substrates including paroxetine. Although clinical evidence of interactions is lacking, plasma concentrations of SSRIs metabolized by CYP2D6 may be increased if bupropion is added. In addition, in vitro studies suggest that paroxetine inhibit the hydroxylation of bupropion. [40993] [4718] [4781] Pemoline: (Major) Drugs which may lower the seizure threshold, such as pemoline, should be used with great caution or avoided in patients taking bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if this combination must be used concurrently; the patient should be closely monitored. [28058] Pentazocine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [56099] (Moderate) Plasma concentrations of opiate agents metabolized by CYP2D6, such as pentazocine, may be increased if bupropion, an inhibitor of the CYP2D6 isoenzyme, is added. Dosage reductions of pentazocine may be needed. Conversely, if bupropion therapy is discontinued, dosages of pentazocine may need to be adjusted upward in some patients. [2173] Pentazocine; Naloxone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [56099] (Moderate) Plasma concentrations of opiate agents metabolized by CYP2D6, such as pentazocine, may be increased if bupropion, an inhibitor of the CYP2D6 isoenzyme, is added. Dosage reductions of pentazocine may be needed. Conversely, if bupropion therapy is discontinued, dosages of pentazocine may need to be adjusted upward in some patients. [2173] Pentobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Perphenazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of perphenazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of perphenazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43070] Perphenazine; Amitriptyline: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of perphenazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of perphenazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43070] (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Phendimetrazine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of phendimetrazine is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Phenelzine: (Severe) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs. [28058] [40993] [41086] [44094] [57922] Phenobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Phenothiazines: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy. [5887] Phentermine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, such as phentermine, may be associated with an increased seizure risk; therefore, seizures may be more likely to occur in patients receiving this weight loss aide with bupropion. Patients should be closely monitored if this combination is necessary. Do not combine therapy with phentermine or phentermine-combinations and bupropion; naltrexone due to this risk and the duplication of therapy for weight loss. [28058] [57922] Phentermine; Topiramate: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, such as phentermine, may be associated with an increased seizure risk; therefore, seizures may be more likely to occur in patients receiving this weight loss aide with bupropion. Patients should be closely monitored if this combination is necessary. Do not combine therapy with phentermine or phentermine-combinations and bupropion; naltrexone due to this risk and the duplication of therapy for weight loss. [28058] [57922] (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Use with caution when topiramate is used for other purposes, as additive CNS reactions may be possible. Pharmacokinetic interactions have not been noted. [27843] [28058] [40993] [41086] [44094] Phenylephrine; Promethazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of promethazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of promethazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43930] Phenytoin: (Moderate) When anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), bupropion should not be used since bupropion lowers the seizure threshold. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions (e.g., neuropathic pain, mood disorders). Bupropion may interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as phenytoin (as well as other hydantoins like fosphenytoin or ethotoin). Monitor for reduced bupropion efficacy. [28058] [28535] [28823] [40993] [41086] [44094] Pimozide: (Severe) Coadministration of pimozide and bupropion is contraindicated due to the potential for increased pimozide exposure. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death. The risk of seizure may also be increased as both drugs lower the seizure threshold. Bupropion is a strong CYP2D6 inhibitor; pimozide is a CYP2D6 substrate. Coadministration of pimozide with another strong CYP2D6 inhibitor increased the pimozide AUC by 151%. [28058] [43463] Pitolisant: (Major) Initiate pitolisant at 8.9 mg once daily in patients taking bupropion; increase pitolisant after 7 days to a maximum dosage of 17.8 mg once daily. If bupropion is initiated in a patient on a stable dose of pitolisant, reduce the pitolisant dose by half. Pitolisant is a CYP2D6 substrate; bupropion is a strong CYP2D6 inhibitor. Coadministration of strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold. [41057] [64562] Prednisolone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Prednisone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Primidone: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Procarbazine: (Severe) There is an increased risk of hypertensive reactions when bupropion is co-administered with monoamine oxidase inhibitors (MAOIs), and the combination is contraindicated. Therefore, concurrent use of bupropion and medications with MAO activity, such as procarbazine, should be avoided. [41086] [45905] Prochlorperazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of prochlorperazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of prochlorperazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [29498] [41057] Promethazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of promethazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of promethazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43930] Propafenone: (Major) Bupropion is an inhibitor of CYP2D6. Concentrations of medications metabolized by CYP2D6, such as propafenone, may be increased if bupropion is added. Dosage reductions of propafenone may be needed. [28058] [28287] Propantheline: (Moderate) Additive anticholinergic effects may be seen when propantheline is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [28714] [29597] [30425] Propoxyphene: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6705] [6993] (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as propoxyphene may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Propranolol: (Minor) Monitor for an increased incidence of propranolol-related adverse effects if bupropion and propranolol are used concomitantly. Coadministration of bupropion and propranolol may result in increased plasma concentrations of propranolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Propranolol is a CYP2D6 substrate. [41057] [53617] Protriptyline: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Ranolazine: (Moderate) Bupropion inhibits CYP2D6. Coadministration of bupropion with medications that are metabolized by CYP2D6, like ranolazine, may result in increased ranolazine plasma concentrations if bupropion is added. [31938] [4718] Rasagiline: (Severe) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs. The manufacturer of rasagiline advises against concurrent use with any antidepressant. [32223] [41086] Remifentanil: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. The usual doses of remifentanil will be ineffective in patients receiving naltrexone. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. However, respiratory depression from remifentanil is not expected to last longer than the effect of a single naloxone dose. Other non-opioid medications should be used prior to, during, and after surgery as increased doses of opiate agonists are required to override the antagonistic effects of naltrexone and may induce prolonged and more severe adverse effects. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] Rifampin: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours. [28001] [32802] Risperidone: (Major) Initiate risperidone at a reduced dose in patients receiving bupropion. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when bupropion is initiated or discontinued. An adjustment of the dose may be required. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. Bupropion is a strong CYP2D6 inhibitor. Risperidone is a CYP2D6 substrate. [41057] [56368] Ritonavir: (Moderate) Concurrent administration of bupropion with ritonavir results in decreased concentrations of bupropion and its active metabolite. According to the manufacturers of bupropion, increased doses of bupropion may be necessary during concurrent therapy; however, the maximum recommended dose of bupropion should not be exceeded. Closely monitor bupropion efficacy if these drugs are given together. Ritonavir induces CYP2B6, which is responsible for bupropion's metabolism. In one study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. In addition, exposure to the active metabolite of bupropion (hydroxybupropion) was decreased by 23%. When given with ritonavir 600 mg twice daily, the AUC and Cmax of bupropion decreased by 66% and 63% respectively and exposure to hydroxybupropion decreased by 78%. [28058] [28315] [34743] [34744] [34745] [34746] [44095] Scopolamine: (Moderate) Additive anticholinergic effects may be seen when scopolamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30354] Secobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Selegiline: (Severe) The manufacturer of bupropion contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with bupropion. After stopping treatment with bupropion, a time period equal to 4 to 5 half-lives of bupropion or any active metabolite should elapse before starting therapy with selegiline. [28058] [40993] [41086] [44094] [57922] Sertraline: (Moderate) Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by CYP2D6 should be approached with caution. Many selective serotonin reuptake inhibitors (SSRIs) are CYP2D6 substrates including sertraline. Although clinical evidence of interactions is lacking, plasma concentrations of SSRIs metabolized by CYP2D6 may be increased if bupropion is added. In addition, in vitro studies suggest that sertraline inhibits the hydroxylation of bupropion. [28001] [40993] [41057] Sodium Oxybate: (Major) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as sodium oxybate. The risk of seizures with bupropion is dose related and is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment If used together, use low initial doses of bupropion and increase the dose gradually. [28528] [41057] Solriamfetol: (Moderate) Monitor for dopamine-mediated effects including nausea, vomiting, dizziness, tremor, and changes in moods or behaviors if solriamfetol, a central dopamine and norepinephrine reuptake inhibitor, is administered with other dopaminergic drugs, such as bupropion. Caution is recommended since this combination has not been evaluated. [64026] Sufentanil: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. The usual doses of sufentanil will be ineffective in patients receiving naltrexone. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. However, respiratory depression from sufentanil is not expected to last longer than the effect of a single naloxone dose. Other non-opioid medications should be used prior to, during, and after surgery as increased doses of opiate agonists are required to override the antagonistic effects of naltrexone and may induce prolonged and more severe adverse effects. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [6993] Tamoxifen: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with bupropion is necessary. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Bupropion is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established. [41057] [63589] Tamsulosin: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as bupropion. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects. [28001] [28058] [29677] Tapentadol: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [36077] [6993] Theophylline, Aminophylline: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as aminophylline. The manufacturer recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, when bupropion is used for smoking cessation, it should be noted that cessation of smoking may result in elevated serum concentrations of some drugs that are hepatically metabolized, such as theophylline or aminophylline, due to lowered induction of hepatic oxidative microsomal enzymes (tobacco smoke induces hepatic enzymes). Downward dosage adjustments of such drugs and more frequent monitoring may be required during smoking cessation. [41086] (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as theophylline. The manufacturer recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, when bupropion is used for smoking cessation, it should be noted that cessation of smoking may result in elevated serum concentrations of some drugs that are hepatically metabolized, such as theophylline or aminophylline, due to lowered induction of hepatic oxidative microsomal enzymes (tobacco smoke induces hepatic enzymes). Downward dosage adjustments of such drugs and more frequent monitoring may be required during smoking cessation. [28058] Thiethylperazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of thiethylperazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of thiethylperazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [62314] Thiopental: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Thioridazine: (Severe) Bupropion is a strong inhibitor of CYP2D6 and the use of thioridazine with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias resulting from elevated serum concentrations of thioridazine. In addition, bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines, such as thioridazine, on lowering the seizure threshold. [41057] [43069] Thiotepa: (Moderate) The concomitant use of thiotepa and bupropion may increase the exposure of bupropion but decrease hydroxybupropion exposure; however, the clinical relevance of this interaction is unknown. Dosage adjustment of bupropion may be necessary based on clinical response. Thiotepa is a CYP2B6 inhibitor in vitro; bupropion is a sensitive substrate of CYP2B6 in vitro. [41057] [61718] Thiothixene: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [41057] Tiagabine: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094] Ticlopidine: (Moderate) Ticlopidine is a potent inhibitor of CYP2B6. By inhibiting this isoenzyme, ticlopidine theoretically could increase the plasma concentrations of drugs that are metabolized by CYP2B6, such as bupropion. Adverse reactions of bupropion, such as tremor, nausea, dry mouth, insomnia, headache, or seizures, may be more likely to occur. [28058] [34691] Timolol: (Minor) Monitor for an increased incidence of timolol-related adverse effects if bupropion and timolol are used concomitantly. Coadministration of bupropion and timolol may result in increased plasma concentrations of timolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Timolol is a CYP2D6 substrate. [28540] [41057] Tobacco: (Moderate) Tobacco contains nicotine as one of its active components, but it is unclear if continuing to smoke concurrently with bupropion use increases the risk of blood pressure elevation. Bupropion has not been reported to interact pharmacokinetically with tobacco when used as monotherapy for smoking cessation; however, when bupropion is used as monotherapy, patients should schedule a date to stop tobacco smoking during the second week of taking bupropion. If the patient is prescribed a combination of bupropion with nicotine replacement therapy (like Nicotine patches) to stop smoking; then the patient should stop Tobacco smoking before starting to use the nicotine replacement therapy. Monitor blood pressure during smoking cessation treatment. [44094] Tolterodine: (Moderate) Bupropion exhibits moderate anticholinergic effects. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with bupropion. [4781] Topiramate: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Use with caution when topiramate is used for other purposes, as additive CNS reactions may be possible. Pharmacokinetic interactions have not been noted. [27843] [28058] [40993] [41086] [44094] Tramadol: (Major) Increased serum concentrations of tramadol and reduced serum concentrations of the O-desmethyltramadol metabolite (M1) would be expected from concurrent use of tramadol and a CYP2D6 inhibitor such as bupropion. As the analgesic activity of tramadol is due to both the parent drug and M1, inhibition of CYP2D6 by bupropion may affect the analgesic effect of tramadol; reduced analgesic effects are possible. Also, administration of tramadol may enhance the seizure risk in patients taking other medications that decrease the seizure threshold such as bupropion. [28001] [28314] Tranylcypromine: (Severe) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs. [28058] [40993] [41086] [44094] [57922] Triamcinolone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Triazolam: (Moderate) Bupropion is contraindicated in patients undergoing abrupt withdrawal of benzodiazepines since the risk of seizures associated with bupropion may be increased. Excessive use of a benzodiazepine is associated with an increased seizure risk upon discontinuation of the drug; seizures may be more likely to occur in these patients during concurrent use of bupropion. [41086] [4781] Tricyclic antidepressants: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Trifluoperazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of trifluoperazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of trifluoperazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43071] Trihexyphenidyl: (Moderate) Additive anticholinergic effects may be seen when trihexyphenidyl is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30336] Trimipramine: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Trospium: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like trospium and bupropion are used concomitantly. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function and temperature regulation. While CNS-related side effects such as drowsiness and blurred vision are not typically noted with trospium, they may occur in some patients. [28058] [29236] Valproic Acid, Divalproex Sodium: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Use with caution when valproic acid and its derivatives (valproate, divalproex) are used for other purposes, as additive CNS reactions may be possible. Pharmacokinetic interactions have not been noted. [27843] [28058] [40993] [41086] [44094] Vigabatrin: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094] Vortioxetine: (Major) The primary isoenzyme involved in the metabolim of vortioxetine is CYP2D6; therefore, the manufacturer recommends a reduction in the vortioxetine dose by one-half during co-administration with strong inhibitors of CYP2D6 such as bupropion. The vortioxetine dose should be increased to the original level when the CYP2D6 inhibitor is discontinued. [56041] Warfarin: (Moderate) When bupropion is used for smoking cessation, be aware that changes in the INR may occur in patients previously stabilized on warfarin as tobacco smoking is reduced or halted, as smoking affects CYP1A2, one of the enzymes involved in warfarin metabolism. Physiological changes resulting from smoking cessation, with or without treatment with bupropion, may alter the pharmacokinetics or pharmacodynamics of certain drugs (e.g.,warfarin) for which dosage adjustment may be necessary. A case report of potential interaction with warfarin and bupropion used for depression has been reported; when bupropion was abruptly halted in the patient prior to surgery, the patient's INR increased to 8.0. The authors could not discern a probable mechanism for the potential interaction, but the patient was also reducing his daily tobacco smoking status, Patients who are receiving warfarin with bupropion should be carefully monitored if the patient is also altering their smoking status. [44094] [62010] Ziprasidone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [28233] [41057] Zolpidem: (Moderate) Rare cases of hallucinations have occurred when zolpidem was administered concurrently with bupropion. Dosage reductions in zolpidem may be needed if bupropion is used concurrently. [28747] Zonisamide: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094]
      Revision Date: 11/18/2020, 06:18:00 PM

      References

      2173 - Lechey D, Gantt C, Lim V. Heparin-induced hypoaldosteronism. JAMA 1981;246:2189-90.4718 - Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein, with Footnotes. In: The Top 100 Drug Interactions - A guide to Patient Management. 2008 Edition. Freeland, WA: H&H Publications; 2008:142-157.4781 - Wellbutrin XL (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2019 Nov.5043 - Ultram (tramadol immediate-release tablets) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 Oct.5542 - Brachtendorf L, Jetter A, Beckurts KT, et al. Cytochrome P450 enzymes contributing to demethylation of maprotiline in man. Pharmacol Toxicol 2002;90:144-9.5887 - Depade (naltrexone hydrochloride tablets, USP) package insert. St. Louis, MO: Mallinckrodt Inc.; 2003 Aug.6365 - Duragesic (fentanyl transdermal system) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 Oct.6705 - Darvocet A500 (propoxyphene napsylate and acetaminophen) package insert. Atlanta, GA: Mikart, Inc.; 2003 Aug.6925 - Reisine T, Pasternak G. Opioid analgesics and antagonists. In: Hardman JG, Limbird LE, Molinoff PB, et al., eds. Goodman and Gilman's the pharmacological basis of therapeutics, 9th edn. New York: McGraw Hill, 1996;521-555.6993 - Revia® (naltrexone hydrochloride) package insert. Pomona, NY: Duramed Pharmaceuticals, Inc.; 2003 Jun.7021 - Lomotil (diphenoxylate hydrochloride and atropine sulfate) tablets package insert. New York, NY: Pfizer Inc.; 2018 Feb.7089 - Codeine sulfate tablets, USP package insert. Columbus, OH: Roxane Laboratories, Inc.; 2003 Oct.7129 - Palladone (hydromorphone hydrochloride extended-release capsules) package insert. Stamford, CT: Purdue Pharma L.P.; 2004 Sep.8203 - Pancof PD (chlorpheniramine, dihydrocodeine, phenylephrine) package insert. Covington, LA: Pamlab, LLC; 2002 Aug.9044 - Cesamet (nabilone) capsule package insert. Somerset, NJ: Meda Pharmaceuticals; 2020 Mar.9282 - Opana ER (oxymorphone hydrochloride) extended-release tablets package insert. Malvern, PA: Endo Pharmaceuticals Inc.; 2019 Oct.24817 - Bryant SG, Guernsey BG, Ingrim NB. Review of bupropion. Clin Pharm 1983;2:525-37.24822 - Robinson DS, Lovenberg W, Keiser H, et al. Effects of drugs on human blood platelet and plasma amine oxidase activity in vitro and in vivo. Biochem Pharmacol 1968;17:109-19.26665 - Reilly KM, Chan L, Mehta NJ, et al. Systemic toxicity from ocular homatropine. Acad Emerg Med 1996;3:868-871.27843 - Ketter TA, Jenkins JB, Schroeder DH, et al. Carbamazepine but not valproate induces bupropion metabolism. J Clin Psychopharmacol 1995;15:327-33.28001 - Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein, with Footnotes. In: The Top 100 Drug Interactions - A guide to Patient Management. 2008 Edition. Freeland, WA: H&H Publications; 2008:142-157.28003 - Mifeprex (mifepristone, RU-486) package insert. New York, NY: Danco Laboratories, LLC; 2019 Apr.28058 - Wellbutrin XL (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2019 Nov.28233 - Geodon (ziprasidone) package insert. New York, NY: Pfizer: 2020 Jan.28262 - Clozaril (clozapine) tablets package insert. Rosemont, PA: HLS Therapeutics (USA), Inc. (Clozaril is a registered trademark of Novartis AG); 2017 Feb.28269 - Celexa (citalopram) package insert. Irvine, CA: Allergan USA, Inc.; 2019 Jan.28280 - Mexiletine capsule package insert. Baudette, MN: ANI Pharmaceuticals, Inc; 2019 Dec.28287 - Rythmol SR (propafenone hydrochloride) capsule extended release package insert. Research Triangle Park, NC: GlaxoSmithKline; 2018 Nov.28314 - Ultram (tramadol immediate-release tablets) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 Oct.28315 - Norvir (ritonavir capsules) package insert. North Chicago, IL: AbbVie Inc; 2020 Oct.28382 - Lotronex (alosetron) package insert. San Diego, CA: Promethus Laboratories, Inc.; 2019 April.28405 - Strattera (atomoxetine) package insert. Indianapolis, IN: Eli Lilly and Company; 2020 Feb.28425 - Flexeril (cyclobenzaprine) package insert. Fort Washington, PA: McNeil Consumer Healthcare; 2013 Apr.28442 - Sustiva (efavirenz) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2019 Oct.28449 - Ramcharitar V, Levine BS, Goldberger BA, et al. Bupropion and alcohol fatal intoxication: case report. Forensic Sci Int. 1992;56:151-6.28455 - Tilton P. Bupropion and guanfacine. J Am Acad Child Adolesc Psychiatry 1998;37:682-3.28519 - Focalin (dexmethylphenidate) package insert. East Hanover, NJ: Novartis Pharmaceutical Corp.; 2007 Apr.28528 - Xyrem (sodium oxybate) oral solution package insert. Palo Alto, CA: Jazz Pharmaceuticals, Inc.; 2020 Sept.28535 - Cerebyx (fosphenytoin sodium) package insert. New York, NY: Pfizer Labs; 2020 Jan.28537 - Coreg (carvedilol) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2017 Sept.28539 - Toprol-XL (metoprolol succinate) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2014 May.28540 - Blocadren (timolol maleate) package insert. Whitehouse Station, NJ: Merck and Co., Inc.; 2002 Mar.28558 - Amoxapine package insert. Parsippany, NJ: Actavis Pharma, Inc.; 2015 Feb.28714 - Johnson AL, Hollister LE, Berger PA. The anticholinergic intoxication syndrome: diagnosis and treatment. J Clin Psychiatry 1981;42:313-7.28747 - Elko CJ, Burgess JL, Robertson WO. Zolpidem-associated hallucinations and serotonin reuptake inhibition: a possible interaction. J Toxicol Clin Toxicol 1998;36:195-203.28785 - Zyprexa (olanzapine, all formulations) package insert. Indianapolis, IN: Eli Lilly and Company; 2020 Apr.28820 - Moban (Molindone) package insert. Chadds Ford, PA: Endo Pharmaceuticals Inc; 2017 Mar.28823 - Tekle A, al-Khamis KI. Phenytoin-bupropion interaction: effect on plasma phenytoin concentration in the rat. J Pharm Pharmacol. 1990;42:799-801.28963 - Omnipaque (iohexol) package insert. Marlborough, MA: GE Healthcare, Inc.; 2020 Jul.28997 - Thorazine (chlorpromazine) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2017 Mar.29236 - Sanctura (trospium tablets) package insert. Irvine, CA: Allergan, Inc.; 2012 July.29498 - Prochlorperazine maleate tablets package insert. North Wales, PA: Teva; 2016 Nov.29597 - Hoffman BB, Lefkowitz RJ. Atropine, scopolamine, and related antimuscarinic drugs. Gilman AG, Rall TW, Nies AS, Taylor P, (eds.) In: Goodman and Gilman's Pharmacological Basis of Therapeutics. 8th ed., New York, Pergamon Press. 1990. 150-61.29677 - Flomax (tamsulosin) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2014 Oct.29796 - Ditropan XL (oxybutynin chloride) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 Sept.29831 - Bethanechol chloride tablet package insert. Parsippany, NJ: Wockhardt USA; 2020 Jun.29882 - Shin YW, Erm TM, Choi EJ, et al. A Case of Prolonged Seizure Activity After Combined Use of Bupropion and Clomipramine. Clin Neuropharmacol. 2004;27:192-94.29934 - Cymbalta (duloxetine hydrochloride) package insert. Indianapolis, IN: Eli Lilly and Company; 2020 May.30072 - Alfentanil hydrochloride injection package insert. Lake Forest, IL: Akorn, Inc.; 2019 Oct.30076 - Brown JH, Taylor P. Muscarinic receptor agonists and antagonists. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG, eds. Goodman and Gilman's the pharmacological basis of therapeutics, 9th edn. New York: McGraw Hill, 1996;141-160.30090 - Bentyl (dicyclomine) package insert. Birmingham, AL: Axcan Pharma US, Inc.; 2018 June.30106 - Imodium A-D Liquid and Caplets (loperamide HCL) consumer product labels. Fort Washington, PA: Johnson and Johnson Consumer Inc., McNeil Consumer Healthcare Division; 2019.30282 - Synalgos-DC (aspirin; caffeine; dihydrocodeine) capsules package insert. Atlanta, GA: Mikart, Inc.; 2019 Oct.30291 - Gao ZG, Liu BY, Cui WY et al. Anti-nicotinic properties of anticholinergic antiparkinson drugs. J Pharm Pharmacol. 1998;50:1299-305.30312 - Cogentin (benztropine mesylate injection) package insert. Lake Forest, IL: Oak Pharmaceuticals, Inc.; 2013 Apr.30336 - Trihexyphenidyl package insert. Lake Forest, IL: VersaPharm Inc.; 2017 Mar.30354 - Transderm Scop 1.5 mg (transdermal scopolamine) package insert. Deerfield, IL: Baxter Healthcare Corporation; 2019 Mar.30355 - Robinul (glycopyrrolate) injection solution package insert. Eatontown, NJ.: West-ward; 2017 Jun.30379 - Hycodan (hydrocodone bitartrate; homatropine methylbromide) package insert. Malvern, PA: Endo Pharmaceuticals Inc.; 2018 Jun.30424 - Pamine/Pamine Forte (methscopolamine bromide) tablet package insert. Melville, NY: PharmaDerm; 2012 Feb.30425 - Brizer DA, Manning DW. Delirium induced by poisoning with anticholinergic agents. Am J Psychiatry. 1982;139:1343-4.30711 - Enablex (darifenacin extended-release tablets) package insert. Irvine, CA: Allergan USA, Inc.; 2016 Sept.30802 - Hansten PD, Horn JR. Top 100 Drug Interactions Monographs. In: The Top 100 Drug Interactions - A guide to Patient Management. 2007 Edition. Freeland, WA: H&H Publications; 2007:4-141.31938 - Ranexa (ranolazine extended-release tablets) package insert. Foster City, CA: Gilead Sciences, Inc. 2019 Oct.32223 - Azilect (rasagiline mesylate) tablets. Kansas City, MO: Teva Neurosciences, Inc.; 2020 Jun.32226 - Cesamet (nabilone) capsule package insert. Somerset, NJ: Meda Pharmaceuticals; 2020 Mar.32231 - Haney M, Bisaga A, Foltin RW. Interaction between naltrexone and oral THC in heavy marijuana smokers. Psychopharmacology 2003;166:77-85.32514 - Atripla (efavirenz; emtricitabine; tenofovir disoproxil fumarate) package insert. Foster City, CA: Gilead Sciences, Inc.; 2019 Oct.32802 - Loboz KK, Gross AS, Williams KM, et al. Cytochrome P450 2B6 activity as measured by bupropion hydroxylation: effect of induction by rifampin and ethnicity. Clin Pharmacol Ther 2006;80:(1):75-84.32916 - Lopressor (metoprolol tartrate) tablets and injection. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2012 Dec.32936 - Invega (paliperidone) package insert. Titusville, NJ: Janssen Pharmaceutica Products, L.P.; 2019 Jan.33363 - Desoxyn (methamphetamine hydrochloride) package insert. Deerfield, IL: Abbott Pharmaceuticals, Inc.; 2017 May.33654 - Codeine sulfate tablets package insert. Eatontown, NJ; West-Ward Pharmaceuticals Corp.: 2019 Oct.34103 - Relistor (methylnaltrexone bromide) tablets and injection solution package insert. Bridgewater, NJ: Salix Pharmaceuticals, Inc.; 2017 Aug.34117 - Entereg (alvimopan) package insert. Lexington, MA: Cubist Pharmaceuticals U.S.; 2020 Nov.34691 - Turpeinen M, Tolonen A, Uusitalo J, et al. Effect of clopidogrel and ticlopidine on cytochrome P450 2B6 activity as measured by bupropion hydroxylation. Clin Pharmacol Ther 2005;77:553-9.34743 - Hesse LM, von Moltke LL, Shader RI, et al. Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion. Drug Metab Dispos 2001;29:100-2.34744 - Hogeland GW, Swindells S, McNabb JC, et al. Lopinavir/ritonavir reduces bupropion plasma concentrations in healthy subjects. Clin Pharmacol Ther 2007;81:69-75.34745 - Kharasch ED, Mitchell D, Coles R, et al. Rapid clinical induction of hepatic cytochrome P4502B6 activity by ritonavir. Antimicrob Agents Chemother 2008;52:1663-9.34746 - Foisy MM, Yakiwchuk EM, Hughes CA. Induction effects of ritonavir: implications for drug interactions. Ann Pharmacother 2008l;42:1048-59.34883 - Promethazine and codeine oral solution package insert. Baudette, MN: ANI Pharmaceuticals, Inc.; 2018 Jun.36077 - Nucynta (tapentadol immediate-release tablets) package insert. Stoughton, MA; Collegium Pharmaceutical, Inc.: 2019 Oct.36146 - Fanapt (iloperidone) package insert. Rockville, MD: Vanda Pharmaceuticals, Inc.; 2017 Mar.36343 - Saphris (asenapine) package insert. St. Loius, MO: Forest Pharmaceuticals, Inc.; 2017 Mar.39635 - Exalgo (hydromorphone hydrochloride) extended-release tablets package insert. Hazelwood, MO: Mallinckrodt Brand Pharmaceuticals Inc.; 2019 Oct.40907 - Torres AR, Whitney J, Gonzalez-Heydrich J. Attention-deficit/hyperactivity disorder in pediatric patients with epilepsy: review of pharmacological treatment. Epilepsy Behav 2008;12:217-33.40944 - Sublimaze (fentanyl citrate injection) package insert. Lake Forest, IL: Akorn, Inc.; 2019 Oct.40993 - Wellbutrin SR (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.41057 - Wellbutrin XL (bupropion) package insert. Bridgewater, NJ: Bausch Health US, LLC; 2019 Nov.41086 - Wellbutrin (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.41087 - Hirschfeld RM, Bowden CL, Gitlin MJ, et al. APA 2002 practice guidelines for the treatment of patients with bipolar disorder; second edition. Accessed December 14, 2016. Available on the World Wide Web at: www.psychiatryonline.org/guidelines.41507 - Loehrer PJ, Kim K, Aisner SC, et al. Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group. J Clin Oncol 1994;12:1164-1168.42227 - Latuda (lurasidone) package insert. Marlborough, MA: Sunovion Pharmaceuticals, Inc.; 2019 Dec.42281 - Cantil (mepenzolate bromide USP) package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2006 Feb.42845 - Abilify (aripiprazole) tablets, discmelt orally-disintegrating tablets, oral solution, and intramuscular injection package insert. Tokyo, Japan: Otsuka America Pharmaceutical, Inc.; 2020 Mar.43067 - Fluphenazine package insert. Princeton, NJ:Sandoz Inc.; 2017 Mar.43069 - Thioridazine package insert. Philadelphia, PA:Mutual Pharmaceutical Company, Inc;2010 Sept.43070 - Perphenazine package insert. Princeton, NJ:Sandoz Inc; 2017 Mar.43071 - Trifluoperazine package insert. Princeton, NJ:Sandoz Inc; 2017 Mar.43463 - Orap (pimozide) package insert. Sellersville, PA: Teva Pharmaceuticals USA; 2014 Mar.43930 - Promethazine hydrochloride solution package insert. Detroit, MI: Caraco Pharmaceutical Laboratories, Ltd.; 2008 Dec.43980 - Ampyra (dalfampridine) extended-release tablets package insert. Hawthorne, NY: Acorda Therapeutics, Inc.; 2016 Oct.44094 - Zyban (bupropion sustained release tablets) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2017 May.44095 - Aplenzin (bupropion extended-release tablet) package insert. Bridgewater, NJ: Sanofi-aventis, LLC.; 2020 May.45206 - Nitro-Dur (nitroglycerin patch) package insert. Orlando, FL: Ingenus Pharmaceuticals, LLC.; 2017 Sept.45905 - Matulane (procarbazine) package insert. Gaithersburg, MD: Sigma-tau Pharmaceuticals, Inc; 2008 Mar.45935 - Gefitinib (Iressa) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018 Aug.46944 - Forfivo XL (bupropion hydrochloride extended-release tablets) package insert. Buffalo, NY: IntelGenx Corp; 2019 Dec.48697 - Korlym (mifepristone) tablet package insert. Menlo Park, CA: Corcept Therapeutics Incorporated; 2017 May.49185 - Acamprosate calcium tablets package insert. Morgantown, WV: Mylan Pharmaceuticals, Inc.; 2019 Jul.51065 - Belviq and Belviq XR (lorcaserin hydrochloride) package insert. Woodcliff Lake, NJ: Eisai Inc.; 2016 Nov.51248 - Hectorol (doxercalciferol) capsules and injection package insert. Cambridge, MA: Genzyme Corporation; 2018 Nov.51664 - Stribild (elvitegravir; cobicistat; emtricitabine; tenofovir disoproxil fumarate) package insert. Foster City, CA: Gilead Sciences, Inc; 2020 Aug.53394 - Abilify Maintena (aripiprazole) extended-release intramuscular injection package insert. Rockville, MD:Otsuka America Pharmaceutical, Inc.; 2020 Feb.53617 - Inderal LA (propranol sustained-release) capsules. Philadelphia, PA: Akrimax Pharmaceuticals. 2012 Jun54802 - Tafinlar (dabrafenib) capsules package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2020 Apr.56041 - Trintellix (vortioxetine tablets) package insert. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2020 Nov.56099 - Revia (naltrexone hydrochloride) package insert. Pomona, NY: Duramed Pharmaceuticals, Inc. 2013 Oct.56303 - Zohydro ER (hydrocodone extended-release capsules) package insert. Morristown, NJ: Currax Pharmaceuticals LLC; 2019 Oct.56361 - Doxorubicin hydrochloride package insert. New York, NY: Pfizer Labs; 2013 Oct.56368 - Llerena A, Berecz R, Penas-Lledo E. Pharmacogenetics of clinical response to risperidone. Pharmacogenomics 2013;14:177-194.56579 - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Updated Mar 10, 2020. Retrieved from the World Wide Web at www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm57419 - Isovue-M (iopamidol) injection package insert. Monroe Township, NJ: Bracco Diagnostics Inc.; 2017 Mar.57877 - Reglan (metoclopramide) oral tablet package insert. Baudette, MN: ANI Pharmaceuticals; 2020 Jun.57922 - Contrave (naltrexone HCl and bupropion HCl) extended-release tablets package insert. La Jolla, CA: Nalpropion Pharmaceuticals, Inc.; 2020 Aug.57937 - Movantik (naloxegol) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020 April.58000 - Tybost (cobicistat) package insert. Foster City, CA: Gilead Sciences, Inc; 2020 Aug.59042 - Cresemba (isavuconazonium) package insert. Northbrook, IL: Astellas Pharma US, Inc; 2019 Dec.59891 - Orkambi (lumacaftor; ivacaftor) tablet package insert. Boston, MA: Vertex Pharmaceuticals, Inc. 2018 August59949 - Rexulti (brexpiprazole) tablets package insert. Rockville, MD: Otsuka Pharmaceutical Co., Ltd.; 2020 Jun.60070 - Evekeo (amphetamine sulfate tablets) package insert. Atlanta, GA: Arbor Pharmaceuticals, LLC: 2015 Apr.60164 - Vraylar (cariprazine capsules) package insert. Parsippany, NJ:Actavis Pharma, Inc.; 2019 May.60196 - Aristada (aripiprazole lauroxil) extended-release intramuscular suspension package insert. Waltham, MA: Alkermes, Inc.; 2020 Feb.60270 - Belbuca (buprenorphine) buccal film package insert. BioDeliviery Sciences International, Inc.: Raleigh, NC; 2019 Oct.60860 - Byvalson (nebivolol and valsartan) tablets package insert. Parsippany, NJ: Actavis Pharma, Inc.; 2016 Jun.60864 - US Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA warns about serious heart problems with high doses of the antidiarrheal medicine loperamide (Imodium), including from abuse and misuse. Retrieved June 7, 2016. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm504617.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery60986 - Briciu C, Neag N, Muntean D, et al. A pharmacokinetic drug interaction study between nebivolol and paroxetine in healthy volunteers. J Clin Pharm Ther. 2014;29:535-540.60987 - Gheldiu AM, Popa A, Neag M, et al. Assessment of potential pharmacokinetic interaction between nebivolol and buproprion in healthy volunteers. Pharmacology. 2016;98:190-198.61718 - Tepadina (thiotepa) injection package insert. Bridgewater, NJ: Amneal Biosciences LLC; 2017 May.61831 - Symproic (naldemedine) package insert. Florham Park, NJ: Shionogi, Inc.; 2018 Jan.61845 - Austedo (deutetrabenazine) tablets package insert. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2019 Jul.62010 - Bavle AD, Phatak AS. Bupropion-warfarin combination: a serious complication. Indian J Psychol Med. 2013;35:311-313.62314 - Torecan (thiethylperazine maleate tablet and injection) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation. 1999 Apr.62642 - Abilify Mycite (aripiprazole oral tablets with sensor) package insert. Rockville, MD: Otsuka America Pharmaceutical, Inc.; 2020 Feb.63161 - Lucemyra (lofexidine) tablets package insert. Louisville, KY: US WorldMeds, LLC; 2018 May.63309 - Epidiolex (cannabidiol) oral solution package insert. Carlsbad, CA: Greenwich Biosciences, Inc.; 2020 Oct.63328 - Aristada Initio (aripiprazole lauroxil extended-release injectable suspension) package insert. Altham, MA:Alkermes, Inc.; 2020 Feb.63368 - Tibsovo (ivosidenib) tablet package insert. Cambridge, MA: Agios Pharmaceuticals; 2019 May.63402 - Azedra (iobenguane I-131) injection package insert. New York, NY: Progenics Pharmaceuticals, Inc.; 2018 July.63529 - Institute for Safe Medication Practices (ISMP). Acute Care ISMP Medication Safety Alert 2018;23:1-2.63589 - Soltamox (tamoxifen) oral solution package insert. Raleigh, NC: Midatech Pharma US Inc.; 2019 April.63790 - Firdapse (amifampridine) tablets package insert. Coral Gables, FL: Catalyst Pharmaceuticals, Inc.; 2018 Nov.64026 - Sunosi (solriamfetol tablets) package insert. Palo Alto, CA: Jazz Pharmaceuticals, Inc.; 2019 Jun.64337 - Vyleesi (bremelanotide) injection package insert. Waltham, MA: AMAG Pharmaceuticals, Inc.; 2020 Oct.64562 - Wakix (pitolisant) tablets package insert. Plymouth Meeting, PA: Harmony Biosciences, LLC; 2020 Oct.64685 - Reyvow (lasmiditan) tablets package insert. Indianapolis, IN: Eli Lilly and Company; 2020 Jul.64768 - Xcorpi (cenobamate) tablets package insert. Paramus, NJ: SK Life Science, Inc.; 2020 Aug.64870 - Dayvigo (lemborexant) tablets package insert. Woodcliff Lake, NJ: Eisai Inc.; 2019 Dec.65169 - Ozanimod (Zeposia) capsules package insert. Summit, NJ: Celgene Corporation; 2020 Sep.65634 - Fintepla (fenfluramine) oral solution package insert. Emeryville CA: Zogenix, Inc.; 2020 Jun.65809 - Olinvyk (oliceridine) injection package insert. Chesterbrook, PA: Trevana, Inc. 2020 Aug.

      Monitoring Parameters

      • blood pressure
      • heart rate
      • LFTs
      • weight

      US Drug Names

      • CONTRAVE

      Global Drug names

      Canada

      • Contrave - (Valeant)

      Czech Republic

      • Mysimba - (PharmaSwiss)

      Denmark

      • Mysimba - (Navamedic)

      Finland

      • Mysimba - (Navamedic)

      Germany

      • Mysimba - (Cheplapharm)

      Ireland

      • Mysimba - (Consilient)

      Netherlands

      • Mysimba - (Orexigen)

      Norway

      • Mysimba - (Orexigen)

      Poland

      • Mysimba - (Valeant)

      Spain

      • Mysimba - (Rovi)

      Sweden

      • Mysimba - (Navamedic)

      United Kingdom

      • Mysimba - (Consilient)